Modification of peripheral micro-vascular reactivity after exertion in patients with systemic sclerosis: blunting the hypertone.

Background: vascular alterations are important features in pathogenesis of Systemic sclerosis (Ssc) being consequence of vascular damage induced by inflammation and promoting tissue damage through an ischemic/ipossic recurrence that enhances fibrotic modifications. The decrease of tissue perfusion due to a progressive capillary reduction must be accompanied and anticipated by significative and progressive alterations of perfusion “quality”. Several authors have demonstrated a progressive decrease in endothelial dependent dilation and reduction in hyperemic function. We hypothesize that also vasodilation due to exercise and sympathetic stimulation may be blunted in these patients with a progressive failure in adaptation to metabolic requests from tissues. Aim: to evaluate the effects on hand cutaneous microcirculation of ischemia, handgrip and exercise in Ssc patients. Methods: we enrolled 12 adult, aged 61±6 y, non-obese, non-smoker, non-diabetic, and non-hypertensive women, who fulfilled the American College of Rheumatology criteria for the diagnosis of SSc. Mean time from diagnosis was 11,5±4,2 y. The were all without ulcers; 2/12 had previous digital ulcers healed . Latest iloprost infusion was at least 28 days before the exams (28-32 days); no pulmonary hypertension signs were detected by means of echocardiography; no vasoactive drugs were assume the day of exams. No obstructive pathology at upper limb was detected using color-Doppler ultrasound, while all had thickening of radial and ulnar vessels with rare dotted calcifications. 6 healthy, age matched subjects were enrolled. We analyzed microcirculatory flux by means of Laser Doppler flowmetry (LD) with probe placed on volar face of the right hand ; flow at humeral artery was measured with ultrasound. Blood pressure was measured with oscillometric device on the some arm at the end of each stimulation. Resistances were calculated as mean pressure/flow . Post ischemic hyperemia was evaluated after 3 minutes ischemia obtained with cuff placed on brachial artery and inflated 20 mmHg over systolic value; hand grip (HG) was determined with fist cluntching on cuff with exerted pressure 70% of maximum for 3 minutes on the other hard; hand exertion (HE) was done with repeated near-maximal fist cluntching for 3 minutes (at least 1 /sec). Data were analyzed with Student’s t test for paired data. Results: LD flow at rest was slightly lower in Ssc (19,7±9,2 vs 25,4±11,7 PU ns); post ischemic hyperemia showed a lower microcirculatory peak flow with LD in Ssc patients (41,5±8,6 vs 65±11,3% increase p<0,05 ); HG determined an increase in LD flow only in healthy (p<0,05), while a slight decrease in Ssc; HE showed an increase in LD flow only in healthy (p<0,05).. Microcirculatory resistances were increased in Ssc patients and slightly reduced only by HG; in healthy they were reduced both by HG and HE. Forearm resistances were significantly lower at rest in healthy (0,64±0,02 vs 1,03±0,06 mmHg/ml/min p<0,05 – figure 2), they were reduced by HG in both groups (p<0,05), while HE reduced them only in healthy (p<0,05); Figure 1: microcirculatory resistances Figure 2: forearm resistances *p<0,05 vs correspondent rest; **p<0,05 vs Ssc patients Conclusions: our study demonstrates that Ssc patient have impairment in microcirculatory flux and increased micro/marco-circulatory resistances at rest. Post ischemic hyperemia and the answer to exertion is impaired in Ssc as well. HG can reduce resistances at the forearm also in Ssc patients with a slight increase in microcirculatory flux. These data show a reduced adaptation Ssc flow regulation when increase in requests occur. HG evokes an noradrenergic stimulation with a better response in Ssc that probably is due to abrupt blunting after sustained stimulation over a chronic hyperactivity, we can also hypothesize positive effect of noradrenaline in reactive vasodilation post-exertion, still working in Ssc. Furthermore HG hyperemia is sustained also by NO production by flow stimulation of endothelial cells. As a conclusion we can hypothesize that HG exertion may be useful in Ssc patients for improving forearm perfusion. References: 1. Della Rossa A, D'Ascanio A, Barsotti S, Stagnaro C, Mosca M. Post-occlusive reactive hyperaemia (POHR) in systemic sclerosis: very early disease (VEDOSS) represents a separate entity compared to established disease. Scand J Rheumatol. 2016 Mar 7:1-4 2. Frech T, Walker AE, Barrett-O'Keefe Z, Hopkins PN, Richardson RS, Wray DW, Donato AJ. Systemic sclerosis induces pronounced peripheral vascular dysfunction characterized by blunted peripheral vasoreactivity and endothelial dysfunction. Clin Rheumatol. 2015 May;34(5):905-13. 3. Waszczykowska A, Goś R, Waszczykowska E, Dziankowska-Bartkowiak B, Jurowski P. Assessment of skin microcirculation by laser Doppler flowmetry in systemic sclerosis patients. Postepy Dermatol Alergol. 2014 Feb;31(1):6-11.