Cardiovascular Journal of Africa: Vol 32 No 5 (SEPTEMBER/OCTOBER 2021)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 32, No 5, September/October 2021 AFRICA 259 clamped by a vascular surgeon at the beginning of a revision joint surgery or resection of a proximal limb tumour. With careful vessel dissection and the minimum pressure required for occlusion, clamp-related complications can be avoided. Interrupting blood flow using an arterial clamp or a tourniquet is associated with haemodynamic changes and leads to inflammation, which triggers pathophysiological processes. 10 Zammert et al . reported that with arterial clamp application, TNF- α played a crucial role in haemodynamic changes and was associated with tissue injury. 11 Although the behaviour of endotoxins after clamping is unclear, Caty et al . showed that TNF- α was involved in the initiation of injury. 12 TNF- α has a central role in initiating an inflammatory response by engaging multiple pathways, especially mitogen- activated protein (MAP) kinases and caspase proteases. MAP kinases increase TNF- α expression and induce a secondary response. 13 Interactions between MAP kinases and TNF- α contribute significantly to tissue regulation for cell response in damage and cellular homeostasis. 14 MAP kinases, also known as stress-response kinases, are triggered by environmental stressors. Mechanical damage of tissue activates the MAP kinase (JNK and p38) pathway stimulated by TNF- α , and activated MAP kinases alter physiological responses in the process of various diseases. 15,16 Activation of JNK has been reported in various pathological conditions such as heart failure and ischaemia–reperfusion injury. In a recent study, authors evaluated images fromhistologically stained tissue sections obtained from rabbit and human atria. 17 In this study, interstitial fibrosis was evaluated by Masson’s trichrome stain. Fibrosis was not expected in our study due to interruption of blood supply for two hours, therefore immunohistochemical examination was not used in our study. Our study indicated that increased TNF- α protein expression was associated with the tourniquet group; although, when all groups were compared with each other, no significant differences were found (Fig. 3). In this scope, our findings suggest that clamp application is favourable to the use of a tourniquet. Longer tourniquet time and higher inflation pressure were associated with higher complication risk. 18 Also, higher age and co-morbidities, such as trauma, peripheral vascular disease and hypertension, elevated the rate of complications. 19 Debates therefore continue about the safety limits associated with pressure and duration. However, most authors suggest that 1.5 to two hours with 200–250 mmHg inflation pressure is appropriate for healthy, normotensive patients. 8 When these safety limits are exceeded, complications may be encountered. 2 Another parameter that affects the pressure is the cuff width. The cuff should be as wide as possible, and it should not encroach upon the surgical site. 2 Contrary to this general belief, a report suggests that muscle damage increases with wide cuffs. 20 There are several reports regarding nerve injury related to the use of tourniquets. 21,22 Nerve tissue is more sensitive to mechanical pressure than muscle tissue, and two studies showed that injury was severe at the proximal and distal edges because of shear stress. 18,22 There was a strong correlation between mechanical pressure duration and nerve injury. Even below 30 minutes of inflation time, paralysis has been reported. Also, after each 30-minute increase in duration, there was a three-fold increase in neurological complications. 22 Muscle tissue is more sensitive to prolonged ischaemia than nerve tissue. Moreover, the injury is severe beneath the cuff. 8 Animal studies have shown that tourniquets are related to decreased muscle force beneath and distal to the cuff and are directly proportional to cuff pressure. 23 Contrary to nerve and muscle complications, vascular complications due to tourniquet use are rare. However, some reports suggest the opposite. For example, Rush et al . found that direct pressure can cause fracture of plaque formation or thrombosis in atherosclerotic vessels. 24 DeLaurentis et al . suggested not to use tourniquets if there is a femoropopliteal aneurysm, femoral–popliteal bypass or calcification. They also concluded that ischaemic pressure necrosis is an additional mechanism of injury. 25 Another report recommends avoiding tourniquet use with poor distal pulses, capillary return or calcified vessels near the application field. 26 However, the reasons for this suggestion (whether because of tourniquet- caused fractures or distortion-traction during surgery) are unclear. 27 Although various types of skin-protection paddings have been produced, skin injury can be encountered at rates of 0.04–0.1%. 28 Tourniquet application therefore has several disadvantages. Nerve and muscle injury are common complications and can occur, even with short inflation times. Complication rates increase when the applied pressure is not adjusted to systemic blood pressure, extremity diameter and cuff width. Tourniquets also require regular calibration and incorrect calibrations can cause serious complications. Vessel complications may be less rare, but additional nerve, muscle and skin complications should be noted. No international quantitative unit can repeatedly be used in experimental studies to measure clamp pressure. 29 In an experimental study, to standardise the clamp pressure between the subjects, the authors noted the lowest notch number at which the clamp did not slip on the vessel but provided transient occlusion. 9 In the same manner, to standardise the pressure, we used the same micro-clamp, which is the smallest available, to occlude the vessel for all subjects. There are also experimental studies examining vessel damage due to clamp application. 9 In an experimental study, four DeBakey vascular clamps were applied to eight carotid arteries of four adult sheep for durations of 15, 30, 45 and 60 minutes, respectively. A significant and ongoing increase in endothelial damage was seen at 15 minutes; the damage was maximal after 30 minutes. The authors concluded that there are four variables to determine the force needed to occlude a vessel: vessel diameter, blood pressure, vessel elasticity and blade contact area. The severity of injury varies according to duration, pressure, intraluminal flow pattern, plaques and vessel elasticity. 9 There are some limitations associated with our study. First, this study did not include a group of participants that were allowed to live after the study (to investigate the late histological changes for both the tourniquet and clamp application). This group of animals could have provided more information about the amount of repair possible over time and would also have shed light on clinical adaptations. However, it is unclear how long subjects should be kept alive to assess long-term effects. Another limitation of the study was that we were unable to compare or equalise the pressures of the tourniquet and the clamp.