Clinical trial NCT04271241: Vascular Function Improvements After Chronic Passive Stretching
Official title: Evidence of Central and Local Vascular Function Improvements After Chronic Passive Stretching
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vasodilation
Vasoconstriction
Stretch
Sympathetic; Imbalance
Keywords: Chronic passive stretching
Central and peripheral arterial stiffness
Blood pressure
Vasomotor response
Crossover effect
Lead sponsor: University of Milan
Sponsor class: OTHER
First posted: 2020-02-17
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Four groups in parallel (three intervention groups and one control) tested at the beginning, during, after and after six weeks (follow-up) from intervention
Primary purpose: TREATMENT

Brief summary: Acutely, during different bouts of passive stretching (PS), blood flow (Q ̇) and shear rate ( ) in the feeding artery of the stretched muscles increases during the first two elongations and then it reduces during the following bouts. This hyperemic response during the first two elongations is mediated by the local release of vasoactive molecules (e.g. nitric oxide, NO). This phenomenon disappears during the following elongations due to the NO and other vasoactive molecule depletion. The relaxation phase between stretching bouts, instead, is always characterized by hyperemia as results of stretch-induced peripheral resistances decrease. Whether chronic PS administration may influence vascular function is still a matter of investigation. The hypothesis is that repetitive PS-induced Q ̇ and changes may be an enough stimulus to provoke increments in NO bioavailability, thus improving vasomotor response.

Detailed description: Vasomotor response is an important marker of cardiovascular health and has been related to cardiovascular co-morbidity. An alteration of vasomotor response, indeed, often precedes an increase in arterial stiffness. By improving and/or maintaining this vascular function, therefore, plays a pivotal role in the prevention of cardiovascular disease. The overall control of the vasomotor response and, in turn, of blood flow distribution in the human body is regulated by two main mechanisms: a systemic control given by the sympathetic nervous system that acts on the arterial smooth muscle fibers causing vasoconstriction, and a local action of vasoactive molecules released by the endothelial cells, such as nitric oxide (NO), leading to vasodilation.

Recent studies report that acute passive stretching (PS), a well-established practice in rehabilitation and sport environments to increase range of motion, may influence the vasomotor response. Specifically, PS provokes two conflicting events: (i) a vasoconstriction with blood flow reduction in the feeding artery of the stretched muscle, triggered by the systemic increase in sympathetic neural tone due to the PS-induced stress on the muscle mechano- and metaboreceptors, and (ii) a vasodilation and subsequent increase in blood flow in the feeding artery due to the prevalence of local vasoactive factors release as a result of the stretch-induced stress applied to the vessel wall, which overwhelms the systemic sympathetic activation. Interestingly, throughout several stretch-shortening cycles, the first acute hyperemic response to stretch described above seems to progressively attenuate until its disappearance during the subsequent stretching cycles, possibly due to NO and other vasoactive molecules depletion.

The shortening phase in between two stretch bouts, instead, is always characterized by hyperemia due to a reduction in the peripheral vascular resistance after the stretch-induced vessels deformation. Possible explanation of these phenomena involves the shear rate, which is the frictional or drag force acting on the inner lumen of the vessels that can trigger a chain of reactions, possibly leading to higher endothelial NO-synthase activity. Continuous and repetitive increases in shear rate induced by PS have been observed to act as vascular training to modulate endothelium remodeling and to improve vasomotor response.

Interestingly, during an acute PS administration, a reduction in blood flow during stretching was described in the contralateral, no-stretched limb. Such a reduction was promptly recovered during the shortening phase. The authors suggested that this occurrence was induced by a systemic sympathetic-mediated vasoconstriction, which was activated by the stretch-induced mechanoreflex.

However, whether chronic PS administration may also affect the vasomotor response in the feeding artery of the contralateral muscle, which was not directly involved in the stretching maneuver, is still an open question.

Together with the changes in local control mechanisms, also possible PS-induced changes in the systemic autonomic control of blood flow has been reported (i.e., reduction in blood pressure and aortic wave reflection magnitude, although its effectiveness remains a matter of debate With this in mind, this study aimed to investigate the effect of PS on the vasomotor response and the stiffness of the arteries directly involved (i.e., femoral and popliteal arteries) and not directly involved (i.e., contralateral femoral and popliteal arteries and brachial artery) with the maneuver applied on the plantar flexors, knee extensor and hip flexor muscles. To this purpose, vasomotor response and arterial stiffness were assessed by Doppler ultrasounds and applanation tonometry, respectively, before and after 12 weeks of PS administration. Hypothesis has been made that repetitive PS bouts, with consequent changes in blood flow and shear rate, may be an effective stimulus to (i) enhance local vasoactive molecules bioavailability in the arteries involved with PS; and (ii) induce a systemic re-modulation of the sympathetic autonomic activity, thus improving arterial compliance and vasomotor response even in those districts not directly involved with PS.

Eligibility criteria: Inclusion criteria:

• None

Exclusion criteria:

* presence of neurological, vascular and musculoskeletal impairments at the lower and upper limbs level;
* being on pharmacological therapy related to either neural and/or vascular response, including hormonal contraceptives and oral supplements;
* being a current or former smoker;
* having an irregular menstrual cycle (26 to 35 days) up to three months before the beginning of the study,
* presenting contraindication for joint mobilization;
* being regularly involved in PS program.

Primary outcomes:
measure: Change from baseline in augmentation Index
timeFrame: Change from baseline in Augmentation Index at 12 weeks
measure: Change from baseline in femoral artery delta blood flow
timeFrame: Change from baseline in Delta Blood Flow at 12 weeks
measure: Change from baseline in brachial artery flow mediated dilation
timeFrame: Change from baseline in brachial artery flow mediated dilation at 12 weeks
Secondary outcomes:
measure: Change from baseline in knee range of motion
timeFrame: Change from baseline in in Knee Range of Motion at 12 weeks
measure: Change in knee extensor muscles maximum isometric voluntary contraction
timeFrame: Before, after 6 weeks, at the end (12th week), and after 6 weeks (Follow-up) of PS training
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Department of Biomedical Science for Health
Study officials:
affiliation: University of Milan
name: Emiliano Cè, PhD
role: PRINCIPAL_INVESTIGATOR
References: