**1. Introduction**

Even as we approach the third decade of the 21st century, cardiovascular disease continues to be the leading cause of death worldwide, accounting for one-third of deaths and being the leading cause of death in Europe [1–4]. More specifically, 4 million Europeans die of cardiovascular disease (CVD) each year (45% of all deaths) [5, 6].

CVDs are a group of disorders that include the heart, blood vessels (arteries, capillaries, and veins), or both [7]. The most common CVDs that are also important for public health are ischemic heart disease, coronary heart disease, and vascular strokes. This category also includes peripheral arterial disease, congenital heart disease, rheumatic heart disease, cardiomyopathy, and cardiac arrhythmias. Gender, age, race, and family history are among the non-modifiable factors of

CVDs, while clinical and behavioral factors are among the modifiable ones. Clinical factors include obesity, hypertension, dyslipidaemia, diabetes mellitus, and cholesterol. Behavioral factors include reduced physical activity, smoking, substance use, unhealthy eating habits and stressful lifestyle as well as the socio-economic level of individuals.

The treatment of these diseases is based mainly on medication of specialized drugs, specific medical invasive techniques, and specialized therapeutic exercises. Therapeutic exercise is one of the most documented approaches for functional rehabilitation of patients with CVD. There is ample research evidence that the recommended levels of exercise are sufficient to prevent ischemic heart disease, stroke, hypertension, and therapeutic exercise adjustments have been investigated to improve their effectiveness, quality of life, and function indicators as well as to reduce morbidity and mortality in patients with CVD [8–13].

Based on the findings of the above research, patients with CVD could benefit significantly if they joined rehabilitation programs using therapeutic exercise. These patients often have low levels of cardiovascular function, muscle mass, and strength [14]. Aerobic exercise as well as low-resistance exercise have been suggested in cardiovascular rehabilitation therapies with positive results in improving the above parameters [15, 16]. Given that high-intensity exercise can cause unwanted cardiovascular adjustments, such as high blood pressure or arrhythmias, it should be avoided in specific patient groups [17, 18]; and low-intensity exercise is identified at levels not exceeding the anaerobic threshold [19].

Low-intensity aerobic exercise has been reported to enhance peripheral circulation, reduce heart attacks and the need for hospitalization, and improve cardiovascular function and quality of life in people with CVD by enhancing their ability to perform daily activities without symptoms or limitations [20]. However, lowintensity aerobic exercise cannot provide adjustments to increase muscle strength and mass [21]; which is why low-resistance exercise is essential and can improve muscle strength, endurance and mass, as well as bone density [22–24].

In recent years, research has demonstrated a novel exercise model, low-load BFRT, which is a therapeutic approach that could lead to significant myodynamic adjustments without the need to apply high tensions and high loads, allowing the implementation of exercise programs even in high-risk groups of patients, such as CVD patients.

BFRT is becoming very popular, and for some scientists it is considered 'the state of art'. Restricting blood flow (not occluding) by itself, or in combination with exercise, results in beneficial adaptations to skeletal muscle and bones in various populations (old, young, trained, untrained). When BFRT is conducted, the blood flow to the exercising muscle is restricted by thin, computer-controlled, pressurized external constricting devices, such as pneumatic cuffs or inflated tourniquets, which are placed at the most proximal part of the arms or legs to reduce the amount of blood flowing back from the muscles in the extremities during a workout.

Historically, BFRT originated in Japan and involves the restriction of blood flow to exercising muscle. It was first described by Dr. Yoshiaki Sato, and the technique is based on blood flow moderation exercise (or vascular occlusion moderation training) involving compression of the vasculature proximal to the exercising muscles by specifically designed equipment. Dr. Sato evolved this technique called KAATSU, which is derived from the combination of the Japanese words for 'additional' (ka) and 'pressure' (atsu) [25]. KAATSU training is also known as vascular occlusion (VO) training. Dr. Sato evolved this technique during the period between 1973 and 1982 and developed various protocols that worked for people in different demographics (elderly, young, athletes, amateurs, etc.). The method was generalized for public use in the 1980s. Soon, the method was used by physicians, manipulative

#### *Blood Flow Restriction Training in Cardiovascular Disease Patients DOI: http://dx.doi.org/10.5772/intechopen.96076*

therapists, acupuncture therapists, moxa therapists, athletic trainers, and physio therapists all over the world.

According to the American College of Sports Medicine (ACSM), a standard conventional training conducted at an intensity of at least 65% + of one-repetition maximum (1RM) is needed to achieve adaptations for muscle hypertrophy.2 Nevertheless there are numerous studies that support low intensity exercise (20%– 40% 1RM) combined with blood flow restriction could be beneficial for stimulating an increase of muscle strength, hypertrophy, and endurance [26–28]. At the same time, the suggested permissible levels of exercise intensity for cardiovascular patients is <30% 1RM, which makes it insufficient to make positive adjustments to increase muscle mass and strength [22, 29].

Approaching exercise with blood flow restriction could be a promising type of exercise for high-risk groups of patients, as research supports that with loads of 20–30% of 1RM, combined with blood flow restriction, it is feasible to yield hypertrophy responses comparable to that observed with heavy-load resistance training [30–32].

Especially in the case of cardiovascular patients where the American Heart Association recommendations currently suggest lower loads and intensity training, 'occlusion exercising' could be a valuable tool in the hands of therapists as it can accelerate patient rehabilitation by minimizing functional deficits in muscle mass and strength that arise during periods of reduced mobility and activity. Therefore, this chapter aims to review all recent literature regarding the impact of low-load BFR resistance training in patients with cardiovascular pathologies on muscle strength and hypertrophy, vascular function, safety, cardiovascular responses, and inflammatory markers.

#### **1.1 Blood flow restriction mechanism of action**

The definitive mechanism by which this kind of exercise provides stimulation for increased muscle strength and mass has not yet been elucidated; however, mechanisms of action of BFR have been reported. The potential physiological mechanisms underlying low-intensity exercise with BFR to improve muscle strength and mass include increased fiber type recruitment, decreased myostatin, stimulation of muscle protein synthesis, and cell swelling, an increase in metabolic stress, which theoretically activates systemic hormone production and fast-twitch muscle fibers, although it is likely that many of the aforementioned mechanisms work together [33]. Specifically, during BFRT, blood flow to the muscle being exercised is mechanically restricted by placing flexible compression cuffs or special straps proximally to the active extremity/extremities (at the upper extremities approximately peripherally at the point of deltoid insertion, at the lower extremities approximately at the top of the thighs peripherally of the gluteal line).

The restriction creates a kind of pressure that reduces blood flow to muscle fibers and, more specifically, to intracellular space. This alters the muscle's biochemistry, increases lactate (lactic acid), and reduces pH, creating a low oxygen supply and intracellular swelling. All the above is thought to threaten the integrity of the cell membrane, which leads to the anabolic response and the increased release of growth hormones [34]. During BFRT, the external pressure applied is sufficient to maintain arterial inflow while occluding venous outflow of blood distal to the occlusion site. It has been suggested that cell swelling, induced by blood-pooling accumulation of metabolites and reactive hyperaemia, is detected by an intrinsic volume sensor, and may consequently lead to an activation of myogenic signaling pathways. This enhanced reperfusion and subsequent intracellular swelling are believed to threaten the structural integrity of the cell membrane, promoting an anabolic response [28].

In addition, during BFRT, there is a limited supply of oxygen to the muscles, which leads to the inactivation of the slow twitch muscle fibers (type I), which need oxygen as an energy source, while on the contrary it contributes to the activation of fast twitch fibers (type II) that have a higher hypertrophic potential than type I [28]. Type II muscle fibers have a relatively larger diameter and higher stimulation threshold. They receive energy mainly from the glycolytic pathway instead of oxidative metabolism, so they are preferentially recruited in a hypoxic environment. Tissue hypoxia from BFRT has been demonstrated to cause preferential recruitment of type II motor units, which typically are only recruited with high-load training [35]. Several studies have shown that the hypoxic intramuscular environment resulting from BFR leads to a high percentage of ATP hydrolysis, pH decrease, lactic acid increase, an increase of heat shock proteins (KSPAs) and protein S6, as well as in the inhibition of myostatin hormone, which inhibits the procedure of muscle mass hypertrophy. The above physiological responses significantly enhance the healing process and muscle hypertrophy [26, 32, 34, 35]. BFRT has also been shown to influence vasculature by promoting postexercise blood flow, oxygen delivery, and angiogenesis. Research indicates that it significantly increases vascular endothelial growth factor (VEGF) expression [36]; promotes vascular function [37]; enhances vascular conductance [52]; and partially alters hemodynamic parameters [38].

### **1.2 Cuff application**

The main goal of the cuff used during BFRT is to provide sufficient pressure to restrict venous outflow while maintaining arterial inflow. Cuff width is a significant factor for determining safe BFRT pressures [39]. Furthermore, wider cuffs require significantly less pressure to achieve arterial occlusion pressure (AOP) [40]. Cuff pressures during BFRT were commonly greater than 200 mm Hg; but recent studies have found that similar positive outcomes could be achieved with pressures as low as 50 mm Hg, with less risk of adverse effects [35]. AOP is defined as the minimum pressure required to stop the flow of arterial blood into the limb. To calculate this, Doppler ultrasonography was placed on the radial or dorsalis pedis artery. The cuff is inflated until no pulse is detected, and then it is slowly released [41]. AOP can vary for each individual, even side-to-side, depending on limb circumference. Recent evidence reports two types of BFRT: personalized and practical. Personalized BFRT utilizes an advanced surgical tourniquet that allows the user to dial in a specific percentage of AOP and maintains this pressure throughout the training session. This has proven beneficial, especially in the research setting where it provides standardized results. On the other hand, practical BFRT includes a blood pressure cuff or elastic band to provide external pressure at a nonspecific value below AOP. Even though practical BFRT is not a standardized method as much as personalized BFRT, there is evidence that shows positive results when used for muscle hypertrophy [42, 43].

#### **1.3 Safety**

As far as safety is concerned, BFR training still requires further discussion, especially when performed with vulnerable people (patients, elderly). The idea of physically restricting blood flow to an extremity may raise red flags, especially regarding the cardiovascular system. It is well known that prolonged ischemia can cause necrosis of muscle tissue. Furthermore, a major concern with BFRT is the potential for thrombus formation [44]; because of the pooling of blood in the extremities. Of the evidence available, systematic reviews of BFR safety indicate it is not associated with additional cardiovascular stresses or morbidity [45–48].

#### *Blood Flow Restriction Training in Cardiovascular Disease Patients DOI: http://dx.doi.org/10.5772/intechopen.96076*

Muscle damage through ischemic-reperfusion injury also occurs when there is blood flow restriction during exercise. Although ischemia reperfusion injury is most associated with long durations of severe ischemia [49]; the combination of short duration BFR with muscle contraction could elevate the possibility of muscle damage with this type of exercise. The risk of muscle damage while using BFRT has been analyzed by several investigations. Creatinine kinase, myoglobin, and interleukin 6 have not been shown to be elevated after BFRT more than traditional exercise [50]. There are case reports where rhabdomyolysis has developed after training; however, it is not known whether BFRT is the causing factor in thrombus formation. A previous survey out of Japan reported a rhabdomyolysis rate of 1 of 12,642 patients [51]. Overall, it appears that muscle damage is a minor risk with BFRT. To date, evidence shows that BFRT is not more risky than high-load resistance training, although careful selection of suitable patients and professional supervision is necessary to reduce the risk of side effects [48].
