Autonomic nerve dysfunction in patients with chronic renal failure has of late become an issue to be investigated. R-R intervals in resting electrocardiograms were measured to evaluate activities of the cardiac parasympathetic nerve system. A total of 140 patients with chronic renal failure were studied to be compared with 20 normal controls (cont.) and 39 with diabetes mellitus (DM). Of these patients 15 were subjected to conservative treatment (CRF), while 125 patients were undergoing hemodialysis due to chronic renal failure-100 of them derived from chronic glomerulonephritis (HD) and 25 from diabetes mellitus (DM.HD). The variation coefficient of the R-R interval (CVRR) was measured after the subject patients had rested for over 15 minutes before a dialysis session. The mean CVRR were 2.15 +/- 1.25% in CRF group, 2.36 +/- 1.37% in HD and 1.37 +/- 0.99% in DM.HD. These values were significantly lower than in control group (4.70 +/- 2.64%). On the other hand, the value in DM.HD group, as shown above, was significantly lower than in HD. In CRF group the CVRR values lowered as residual renal functions decreased. No significant correlations between CVRR S and the duration of hemodialysis treatment were noted among the groups. In HD group the CVRR S were significantly lower in patients with hypotensive tendency during hemodialysis than in those who enjoyed good control of blood pressure. These results suggest that the measurement of CVRR S can be of help in evaluating autonomic nerve dysfunction in patients with chronic renal failure.
To the practicing clinician, it seems obvious that limb hemodynamics would be the primary determinant of walking distance. However, other determinants, such as skeletal muscle metabolism, may play a role. Accordingly, in the current study, we examined the relationship between measures of limb hemodynamics and walking capacity in patients with peripheral arterial disease (PAD). We measured toe and ankle pressures for calculation of toe-(TBI) and ankle (ABI)-brachial indices; basal and hyperemic calf blood flow (CBF; by plethysmography); and initial (ICT) and absolute (ACT) claudication time using the Skinner-Gardner protocol. As expected, PAD patients had impaired limb hemodynamics with reduced TBI, ABI and a reduction in ABI post-exercise. However, there was no relationship between any of the hemodynamic variables (including ABI, ABI reduction post-exercise, TBI, baseline or maximal CBF) and walking distance as assessed by ICT or ACT. A subset of PAD patients with an ACT >750 s (n =16; ‘long claudicators’) were compared with a subset of PAD patients with an ACT <260 s (n = 16; ‘short claudicators’). The average ACT in the long claudicants was over fivefold greater than the short claudicators. Surprisingly, there were no differences between the two groups in any of the hemo-dynamic variables. There was also no relationship between the initial ABI, TBI, toe pressure, baseline or hyperemic CBF, and the improvement in ACT over the 3-month course of the study. This study found little relationship between hemodynamic variables and functional capacity in PAD. Accordingly, to assess the response to therapeutic interventions, exercise performance and functional status need to be directly measured, and cannot be predicted from hemodynamic measurements.
L-arginine is the precursor of endothelium-derived nitric oxide, an endogenous vasodilator. L-arginine supplementation improves vascular reactivity and functional capacity in peripheral arterial disease (PAD) in small, short-term studies. We aimed to determine the effects of long-term administration of L-arginine on vascular reactivity and functional capacity in patients with PAD.The Nitric Oxide in Peripheral Arterial Insufficiency (NO-PAIN) study was a randomized clinical trial of oral L-arginine (3 g/d) versus placebo for 6 months in 133 subjects with intermittent claudication due to PAD in a single-center setting. The primary end point was the change at 6 months in the absolute claudication distance as assessed by the Skinner-Gardner treadmill protocol. L-arginine supplementation significantly increased plasma L-arginine levels. However, measures of nitric oxide availability (including flow-mediated vasodilation, vascular compliance, plasma and urinary nitrogen oxides, and plasma citrulline formation) were reduced or not improved compared with placebo. Although absolute claudication distance improved in both L-arginine- and placebo-treated patients, the improvement in the L-arginine-treated group was significantly less than that in the placebo group (28.3% versus 11.5%; P=0.024).In patients with PAD, long-term administration of L-arginine does not increase nitric oxide synthesis or improve vascular reactivity. Furthermore, the expected placebo effect observed in studies of functional capacity was attenuated in the L-arginine-treated group. As opposed to its short-term administration, long-term administration of L-arginine is not useful in patients with intermittent claudication and PAD.
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