Our results in the present
in vivo study using NIRS to investigate changes in skeletal muscle oxygenation and blood flow, microvascular compliance, and mVO
2 during haemodialysis provide two major findings. The first finding is that although haemodialysis left StO
2 unchanged in both groups, it strongly influenced Hb tissue concentrations and micro-vascular compliance. Haemodialysis invariably caused greater changes in patients with diabetes than in those without. A second new finding in patients with diabetes was that, as well as changing tissue haemoglobin concentration and micro-vascular compliance, haemodialysis altered tissue blood flow (mHF and mBF), tissue oxygenation (CtO
2) and the metabolic rate (mVO
2). A secondary finding was that at baseline (before haemodialysis) NIRS disclosed no differences in the measured tissue variables in patients with and without diabetes, whereas in patients with diabetes the baseline values of microvascular compliance were higher than those in the healthy control group (Table
4). These findings may help to explain how haemodialysis influences muscular performance.
Skeletal muscle oxygenation
Our findings in the present study dictate two conclusions. First - at least in the patients we studied, who had no signs of cardiac or respiratory failure - dialysis leaves skeletal muscle oxygenation unchanged. Second, instead of worsening the CtO2 further, dialysis increases the oxygen content in diabetic persons and does so by increasing [HbO2] and muscular tissue blood flow. Third, CtO2 increases during dialysis, probably because dialysis reduces factors hindering oxygen availability - in particular, the tissue water content.
Our NIRS findings showing that haemodialysis leaves skeletal muscle oxygenation unchanged argue against previous studies reporting reduced oxygenation during haemodialysis [
26,
27].
Oxygenation during dialysis has been previously assessed in various ways and in various tissues. The data obtained in humans with transcutaneous partial pressure of oxygen monitoring [
27] show that oxygenation falls dramatically during dialysis and remains low for at least 4 hours thereafter. Previous studies also reported a 5 to 15% fall in the partial pressure of oxygen in arterial blood within about 30 to 60 minutes after dialysis began that persisted throughout the session [
28]. The measurements of the oxygen tension could be influenced by the acetate in the dialysis fluid, or by the patients' cardiopulmonary status [
29], or by both. Although to avoid arterial cannulation in patients attending the daycare clinic we did not obtain serial measurements of the partial pressure of oxygen in arterial blood, neither of these factors influenced our results because our patients were dialyzed with bicarbonate fluid and we excluded patients who had signs of cardiac or respiratory failure. Furthermore, the discrepancy between the oxygen tension measurements and the Hb oxygenation rate measured by NIRS can be fully explained considering that these variables reflect different types of oxygenation differently affected by fluid removal.
The absence of differences between the studied variables in the two groups of patients could depend on the small study sample and the higher variability in patients without diabetes than in those with diabetes. Unlike other studies, we measured absolute skeletal muscle oxygenation during dialysis non-invasively in patients at rest. Predialysis tissue oxygen content HbO2 and CtO2 values were nevertheless lower in patients with diabetes than in healthy subjects, and dialysis for 1 hour was sufficient to annul the difference.
Previous data obtained with NIRS technology already document higher Hb desaturation in patients with peripheral vascular disease and diabetes during exercise [
30]. In theory, the reduced baseline skeletal muscle oxygenation (HbO
2, StO
2 and CtO
2) we detected in patients with diabetes at rest could be related to the microangiopathy typical of diabetes [
31].
The reduced oxygenated Hb concentration shown in both groups of patients could reflect the lower arteriolar and capillary vascular compared with the venular bed. These micro-vascular changes reverse during haemodialysis (Table
4).
Even though StO
2 predialysis values were lower in patients with diabetes than in healthy controls, haemodialysis left StO
2 unchanged in both groups of patients studied. The absence of changes in StO
2 despite marked changes in tissue [HbT], [HHb] and [HbO
2] - reflecting changes in the vascular bed, blood flow and mVO
2 - confirms that StO
2 (percentage tissue oxygenation) is not merely a variable indicating the balance between blood flow and oxygen extraction. StO
2 depends critically on the tissue vascular bed, whose volumes vary substantially under healthy and pathological conditions [
32].
Our NIRS findings also extend current knowledge on the
in vivo dialysis-induced changes in the skeletal muscle blood flow. Ample research on systemic haemodynamics during haemodialysis already shows, even in haemodynamically stable subjects, a reduction in cardiac output and oxygen supply, and indirectly an increase in systemic vascular resistance [
14]. These systemic changes led the investigators to conclude that haemodialysis induces peripheral hypoperfusion [
33].
Although we cannot compare our findings in patients with diabetes and studies investigating other groups of patients, the increased calf blood flow that NIRS documented in our patients without diabetes seemingly contrast with micro-neurographic data on the increased sympathetic activity [
34].
A possible reason for this discrepancy is that dialysis increases the [HHb] and [HbO
2] variables, reflecting changes in the numbers of capillaries, arteriovenous shunts, postcapillary venules and, to a lesser extent, the arterioles [
35]. These vascular bed changes might in theory be accompanied by increased neuronal sympathetic activity that could leave overall local tissue blood flow unchanged.
Microvascular bed
A finding that extends current knowledge on the
in vivo effects of haemodialysis was that the volume and distribution of the microvascular bed increased in both groups of dialyzed patients. Our data corrected for vascular Hb changes (Table
2) exclude the possibility that Hb concentrations increase because dialysis removes excess fluid within vessels, and suggest that dialysis removes body fluids outside the vessels, thus reducing interstitial oedema [
36], and at the same time reduces external compression on the microcirculation. Vasodilation could also arise from dialysis-induced inflammation through complement factor activation and vascular endothelial production of cytokines and prostacyclin [
37].
Another reason for vasodilation is that many of our subjects were taking vasoactive drugs. Calcium antagonists, angiotensin-converting enzyme inhibitors, and α-antagonists might therefore have helped to amplify the response to dialysis-induced fluid removal, especially given that patients taking these agents were mostly diabetic individuals. Even though we excluded patients who had a history of autonomic nervous system dysfunction or experienced hypotensive episodes during dialysis, we cannot exclude the possibility that the abnormal vasodilation especially in patients with diabetes depended on autonomic dysregulation. Neither autonomic dysfunction nor medications nevertheless brought about a reduction in arterial pressures that could have distinguished between the two study groups.
Oxygen supply/consumption relationship
Even though haemodialysis increased tissue [HHb] and reduced microvascular compliance in both groups of patients studied, only in those patients with diabetes did dialysis lead to increased blood flow, HbO2, CtO2 and mVO2. The increased blood flow was presumably due to the augmented arteriolar and capillary bed. Because we studied patients at rest, the increased oxygen availability was presumably not the consequence but the cause of the increased muscle-tissue metabolic rate.
Our NIRS findings on the tissue effects induced by haemodialysis in patients with diabetes also provide useful information on the relationship between oxygen consumption and supply. An interesting finding was that even though dialysis left StO2 statistically unchanged, the increased cell metabolism was correlated to the increase of blood supply. In our study, we observed no changes in oxygen supply other than those related to the dialytic therapy itself - showing that, in the skeletal muscle of diabetic patients with chronic renal failure at rest, dialysis reverses the mVO2 limited by blood flow supply. Why we found a relationship between blood flow and oxygen consumption only in diabetic subjects remains to be clarified.
Although dialysis was not shown to modify cell metabolism in patients without diabetes, the correlation between, on one hand, the reduced microvascular compliance and, on the other hand, the deoxygenated Hb tissue concentration and the increased tissue oxygen consumption seems to confirm the role of fluid removal during dialysis [
39] as a factor facilitating cell metabolism.