Bilateral Common Carotid Artery Ligation in Sheep. Could These Animals Be Used As Human Models for Vascular and Cerebral Research?
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Acta Veterinaria-Beograd 2017, 67 (4), 459-476 UDK: 636.32/.38.028:616.133-089-092.8 DOI:10.1515/acve-2017-0038 Research article BILATERAL COMMON CAROTID ARTERY LIGATION IN SHEEP. COULD THESE ANIMALS BE USED AS HUMAN MODELS FOR VASCULAR AND CEREBRAL RESEARCH? PODLAHA Jiří1*, SCHWANHAEUSER Kräuff2, KADEŘÁBKOVÁ Tereza3 1Department of Surgery, University Hospital Brno Bohunice, Faculty of Medicine, Masaryk University, Brno, Czech Republic; 2Department of Preventive Medicine / Public Health, Faculty of Medicine, Masaryk University, Brno, Czech Republic; 3Department of Anaesthesiology Resuscitation and Intensive Care Medicine, University Hospital Brno Bohunice, Brno, Czech Republic. (Received 19 February, Accepted 07 June 2017) Experimental animals are still used in today’s medicine to understand better physiological or pathological processes, or to develop, for example better vascular prostheses. For that reason, these animals must show some similarities with humans, from the anatomical to the physiological point of view. When developing vascular prostheses, we have to evaluate if the graft will react in the expected way and if during experimental research there will be some factors that might infl uence the proper functioning of vascular prostheses in the human body. We observed the consequences of bilateral common carotid artery ligation (BCCAL) or Sham operation in seventeen healthy Merinolandschaf / Württemberg sheep, aged between 2 and 4 years, after testing new types of carbon-coated ARTECOR® and ADIPOGRAFT Ra 1vk 7/350 vascular prostheses. After the follow-up period the prostheses were extirpated, so the blood supply was provided from the vertebral arteries. Sheep in both groups were not sacrifi ced, but were observed for 18 months. After the observation period all sheep showed no physical or neurological changes and all are still alive. Animal responses to BCCAL are different, depending on the animal species, age, and condition. In sheep, bilateral blocking of the blood fl ow in the carotid bed seems to be conceivable since the brain was suffi ciently supplied with blood from the vertebral arteries. Key words: bilateral common carotid artery ligation (BCCAL), circle of Willis, common carotid artery, sheep survival, Shechita, Dhabihah, Kosher or Halal quality meat INTRODUCTION Is sheep able to survive bilateral ligation of the common carotid artery (BCCAL)? This question arose as a secondary issue during the experimental assessment of the new type of vascular prostheses (carbon-coated ARTECOR® and ADIPOGRAFT Ra *Corresponding author: e-mail: [email protected] 459 Acta Veterinaria-Beograd 2017, 67 (4), 459-476 1vk 7/350 with Adiponectin) developed at the Knitting Research Institute, a. s. Brno, Czech Republic. The aim of this study was to compare the consequences of bilateral common carotid artery ligation in sheep with those observed in humans, in order to determine if sheep are the ideal animal model for cerebrovascular experimental surgery, as other animals are used for other types of experimental surgeries due to their similarities with humans [1]. Experimental and model animals have been used, by the Greek physician and surgeon Claudius Galenus (129-200 AD), and later by William Harvey (1578-1658 AD) [1]. Nowadays rats, mice, guinea pigs, rabbits, cats, dogs, sheep, pigs, monkeys, are used for surgical / vascular training [2-4], as well as experimental animals [1,5-13]. They are chosen due to their availability, handling, anatomical / physiological similarity with human beings, adaptability to physiological changes, and from the vascular point of view, due to the vessel caliber and the ability to model human responses [1,5-8,12]. Despite similarities to the human anatomy, animal models are unable to reproduce exactly the complex physiological human features [1,5-8,13-18]. Sheep are commonly used as animal models in vascular prosthetic research, mainly for carotid artery, and for many years they have served as the gold standard for cardiovascular bioprosthetic evaluation studies [1,5-8,13,15,18]. Their acquisition cost is low, they are easy to maintain, and their anatomical properties (long necks for easy and simple surgical access for vascular prostheses implantation / explantation and their carotid arteries have a similar diameter to those observed in humans) are suitable for vascular prostheses implantation and monitoring [1,5,6,8,11,12]. Sheep c oagulation is very similar to humans in comparison to dogs or pigs [1,5], despite the fact that sheep have a higher number of thrombocytes than most species used as experimental animals, having a tendency to hypercoagulation [1]. It was proved that PT, APTT, activated coagulation time, thrombocyte counts and their aggregation are not infl uenced neither by anesthesia nor by surgery, except for heparin administration [1,19-20]. From the vascular anatomical, hemodynamic and hematological point of view, humans and sheep differ as presented in Table 1 [1] and Table 2 [1]: Table 1. Common carotid artery anatomical and physiological differences between human and sheep Diameter Mean fl ow Mean velocity Mean WSS (mm) (mL/min) (cm/s) (dynes/cm2) Human 1, 34 6.5 - 7.0 455 - 483 22.3 - 24.4 7.8 Sheep 1 5.6 - 7.2 325 16.8 8.4 All values are expressed as mean or range 460 Podlaha et al.: Bilateral common carotid artery ligation in sheep. could these animals be used as human models for vascular and cerebral research? Table 2. Haemodynamic and haematological differences between human and sheep RCB Plt WBC SBP DBP HR TBV (x109 /mL) (x109 /mL) (x109 /mL) Human 1, 34 126 ± 14 79 ±10 70 ± 14 80 4.8 - 5.4 265 ± 135 7.4 ± 3.4 Sheep 1 140 90 95 ±24 58 10.0-13.0 550 ± 250 8 ± 4 SBP – systolic blood pressure (mm Hg); DBP – diastolic blood pressure (mm Hg); HR – heart rate (beats / min); TBV – total blood volume (mL/Kg); RCB – red blood cell count; Plt, – platelet count; WBC – white blood cell count. All values are expressed as mean ± standard deviation or range. Anatomical overview. Human brain vascular supply: The human brain is supplied in 80- 85% by the two internal carotid arteries and in 15-20% by the two vertebral arteries [21,22]. Both vertebral arteries merge to become the basilar artery before entering the so-called circle of Willis together with both internal carotid arteries. The circle of Willis provides collateral blood fl ow to the brain. The right and left vertebral arteries branch off the right and left subclavian arteries while the right and left carotid arteries arise from the right and left common carotid arteries [21,22]. Blood is then taken into the brain by the basilar artery which gives off the right and left posterior cerebral arteries. Communicating arteries complement the circle of Willis and then branch off the anterior, medial and posterior arteries. The posterior communicating artery is given off as a branch of the internal carotid artery just before it divides into its terminal branches: the anterior and middle cerebral arteries. Furthermore, the anterior cerebral artery forms the anterolateral portion of the circle of Willis, while the middle cerebral artery does not contribute to the circle of Willis [21]. The importance of the circle of Willis relies on collateral circulation to supply the brain in the case that the main arteries stenose or occlude, so the blood fl ow from other arteries can maintain brain perfusion [23]. It is important to state that the entire brain blood supply comes from these arteries. Sheep brain vascular supply: the circle of Willis is observed in mammals but its supply and fl ow volumes might vary among different species [15,24-27]. This is an important fact at the time of experimentation, because a stenosed or ligated artery might have different consequences. [15,24-27]. In sheep, the brain is supplied as in humans by two carotid and two vertebral arteries [15,24-27]. The internal carotid arteries arise from the common carotid arteries. Both penetrate the skull at the Fissura sphenopetrosa and end up at the rete mirabile epidurale rostrale. At its caudal part, the branches of the vertebral arteries, condillary artery, and the medial meningeal artery from the occipital artery enter bilaterally. The rete epidurale has important connections with the maxillary artery [25,27].The circle of Willis is formed by the cerebral carotid arteries, which caudally end as the Arteria spinalis vertebralis [24,26,27]. The v ertebral arteries arise from the Truncus costocervicalis and run cranially through the Canalis transversarium up to the third and second vertebrae. On its way to the neck it gives off the Ramus spinalis which passes through the foramen intervertebrale into the canalis spinalis. Its branch, 461 Acta Veterinaria-Beograd 2017, 67 (4), 459-476 ramus medullaris, goes into the subarachnoideal space and here it joins the A. spinalis ventralis [24,25,27]. Between the second and the third vertebrae, the A. vertebralis splits into a thick lateral stem, which initially runs through the foramen transversarium axialis, then continuing through the foramen vertebrale laterale it pierces the canalis spinalis where it joins the strong intravertebral stem [24,25,27]. This artery together with the rami spinales and in the skull with the branches of the Arteria maxillaris (in foetuses also with the A. carotis interna) forms the epidural network. The medial branch of the A. vertebralis anastomoses to its contralateral part and once it passes the atlas, it splits into a medial fi nal branch, which it joins to its contralateral branch, or forms with it a network which opens into the rete mirabile caudale on the skull base. In most cases these are connected to the A. condylaris [25]. Baldwin and May studied the brain arterial supply in sheep too [28-31]. They pr oved on latex colored vessels, connections between A.