Damage to visual pathways can lead to irreversible blindness. Posterior visual pathways, located within a watershed area, are predisposed to hypoperfusion/reperfusion injury. In a novel rat model of bilateral common carotid artery occlusion (BCCAO), oxidative injury to the superior colliculus (SC), a major visual center within the watershed area was evaluated, in addition to its effects on retinal ganglion cells (RGCs). Nitrotyrosine, a footprint of peroxynitrite-mediated oxidative injury in the SC, and microtubule-associated protein 2, a dendrite marker in the retina, were assessed using immunofluorescence and confocal microscopy. Nitrotyrosine-immunoreactivity in the SC was increased 2 weeks after BCCAO compared to controls. Microtubule-associated protein 2-immunoreactivity in the central inner plexiform layer was reduced 3 weeks after BCCAO compared to controls. Global incomplete cerebral hypoperfusion/reperfusion induced oxidative injury in the SC and retrograde RGC dendritic changes. This suggests that cerebrovascular injury affecting the posterior visual pathways may contribute to vision loss in patients.

Damage to visual pathways can lead to irreversible blindness. Posterior visual pathways, located within a watershed area, are predisposed to hypoperfusion/reperfusion injury. In a novel rat model of bilateral common carotid artery occlusion (BCCAO), oxidative injury to the superior colliculus (SC), a major visual center within the watershed area was evaluated, in addition to its effects on retinal ganglion cells (RGCs). Nitrotyrosine, a footprint of peroxynitrite-mediated oxidative injury in the SC, and microtubule-associated protein 2, a dendrite marker in the retina, were assessed using immunofluorescence and confocal microscopy. Nitrotyrosine-immunoreactivity in the SC was increased 2 weeks after BCCAO compared to controls. Microtubule-associated protein 2-immunoreactivity in the central inner plexiform layer was reduced 3 weeks after BCCAO compared to controls. Global incomplete cerebral hypoperfusion/reperfusion induced oxidative injury in the SC and retrograde RGC dendritic changes. This suggests that cerebrovascular injury affecting the posterior visual pathways may contribute to vision loss in patients.

Objetivo: Desenvolver um modelo experimental estável de aneurisma sacular em carótida de suínos utilizando veia jugular interna. Materiais e Métodos: Em 12 suínos sadios, com peso variando entre 25 e 50kg, sendo 5 machos e 7 fêmeas, foi confeccionado aneurisma na artéria carótida comum direita. Após arteriotomia elípitica foi realizada anastomose término-lateral com coto distal de veia jugular interna. O volume do aneurisma era calculado de maneira que o valor não excedia em 27 vezes o valor da área da arteriotomia. Após 6 dias era realizada angiografia e a análise microscópica dos aneurismas para avaliar perviedade, trombose parcial ou total dos mesmos. Resultados: Houve ganho de peso significante dos suínos no intervalo de tempo entre a confecção do aneurisma e a angiografia (p=0,04). Foi observada perviedade aneurismática em 10 suínos (83%). Ocorreu infecção de ferida operatória em 2 animais (16,6%) ambas com início de aparecimento 3 dias após a confecção do aneurisma. Após análise histológica dos aneurismas, foram detectados trombos ocluindo parcialmente a luz aneurismática em 9 suínos (75%). Nesses animais observou-se que em média 9% da luz aneurismática estava preenchida por trombos. Conclusão: O modelo experimental estável de aneurisma sacular em carótida de suínos utilizando veia jugular interna foi desenvolvido. / Purpose: To develop an stable experimental model of carotid artey saccular aneurysm in swine using the internal jugular vein. Methods: In 12 healthy swines, weighing between 25 and 50kg, 5 males and 7 females, aneurysms were made aneurysm in the right common carotid artery. After elliptical arteriotomy it was made end-to-side anastomosis with the distal stump of the internal jugular vein. The volume of aneurysms was calculated in a way that the value did not exceed on 27 times the value of the area of arteriotomy. After six days was performed angiography and microscopic analysis of aneurysms to assess patency, partial or total thrombosis of them. Results: There was a significant weight gain of swines in the time interval between the making of the aneurysm and angiography (p = 0.04). Aneurysmal patency was observed in 10 swines (83%). Wound infection occurred in 2 animals (16.6%) both with early onset 3 days after making of the aneurysm. After histological analysis of aneurysms, thrombus were founded partially occluding the light aneurysm in 9 animals (75%). In these animals it was observed that in average 9% of the aneurysmal lumen was filled with thrombus. Conclusion: The stable experimental model of carotid artey saccular aneurysm in swine using the internal jugular vein was developed.

Objetivo: Desenvolver um modelo experimental estável de aneurisma sacular em carótida de suínos utilizando veia jugular interna. Materiais e Métodos: Em 12 suínos sadios, com peso variando entre 25 e 50kg, sendo 5 machos e 7 fêmeas, foi confeccionado aneurisma na artéria carótida comum direita. Após arteriotomia elípitica foi realizada anastomose término-lateral com coto distal de veia jugular interna. O volume do aneurisma era calculado de maneira que o valor não excedia em 27 vezes o valor da área da arteriotomia. Após 6 dias era realizada angiografia e a análise microscópica dos aneurismas para avaliar perviedade, trombose parcial ou total dos mesmos. Resultados: Houve ganho de peso significante dos suínos no intervalo de tempo entre a confecção do aneurisma e a angiografia (p=0,04). Foi observada perviedade aneurismática em 10 suínos (83%). Ocorreu infecção de ferida operatória em 2 animais (16,6%) ambas com início de aparecimento 3 dias após a confecção do aneurisma. Após análise histológica dos aneurismas, foram detectados trombos ocluindo parcialmente a luz aneurismática em 9 suínos (75%). Nesses animais observou-se que em média 9% da luz aneurismática estava preenchida por trombos. Conclusão: O modelo experimental estável de aneurisma sacular em carótida de suínos utilizando veia jugular interna foi desenvolvido. / Purpose: To develop an stable experimental model of carotid artey saccular aneurysm in swine using the internal jugular vein. Methods: In 12 healthy swines, weighing between 25 and 50kg, 5 males and 7 females, aneurysms were made aneurysm in the right common carotid artery. After elliptical arteriotomy it was made end-to-side anastomosis with the distal stump of the internal jugular vein. The volume of aneurysms was calculated in a way that the value did not exceed on 27 times the value of the area of arteriotomy. After six days was performed angiography and microscopic analysis of aneurysms to assess patency, partial or total thrombosis of them. Results: There was a significant weight gain of swines in the time interval between the making of the aneurysm and angiography (p = 0.04). Aneurysmal patency was observed in 10 swines (83%). Wound infection occurred in 2 animals (16.6%) both with early onset 3 days after making of the aneurysm. After histological analysis of aneurysms, thrombus were founded partially occluding the light aneurysm in 9 animals (75%). In these animals it was observed that in average 9% of the aneurysmal lumen was filled with thrombus. Conclusion: The stable experimental model of carotid artey saccular aneurysm in swine using the internal jugular vein was developed.

Objetivo: Desenvolver um modelo experimental estável de aneurisma sacular em carótida de suínos utilizando veia jugular interna. Materiais e Métodos: Em 12 suínos sadios, com peso variando entre 25 e 50kg, sendo 5 machos e 7 fêmeas, foi confeccionado aneurisma na artéria carótida comum direita. Após arteriotomia elípitica foi realizada anastomose término-lateral com coto distal de veia jugular interna. O volume do aneurisma era calculado de maneira que o valor não excedia em 27 vezes o valor da área da arteriotomia. Após 6 dias era realizada angiografia e a análise microscópica dos aneurismas para avaliar perviedade, trombose parcial ou total dos mesmos. Resultados: Houve ganho de peso significante dos suínos no intervalo de tempo entre a confecção do aneurisma e a angiografia (p=0,04). Foi observada perviedade aneurismática em 10 suínos (83%). Ocorreu infecção de ferida operatória em 2 animais (16,6%) ambas com início de aparecimento 3 dias após a confecção do aneurisma. Após análise histológica dos aneurismas, foram detectados trombos ocluindo parcialmente a luz aneurismática em 9 suínos (75%). Nesses animais observou-se que em média 9% da luz aneurismática estava preenchida por trombos. Conclusão: O modelo experimental estável de aneurisma sacular em carótida de suínos utilizando veia jugular interna foi desenvolvido. / Purpose: To develop an stable experimental model of carotid artey saccular aneurysm in swine using the internal jugular vein. Methods: In 12 healthy swines, weighing between 25 and 50kg, 5 males and 7 females, aneurysms were made aneurysm in the right common carotid artery. After elliptical arteriotomy it was made end-to-side anastomosis with the distal stump of the internal jugular vein. The volume of aneurysms was calculated in a way that the value did not exceed on 27 times the value of the area of arteriotomy. After six days was performed angiography and microscopic analysis of aneurysms to assess patency, partial or total thrombosis of them. Results: There was a significant weight gain of swines in the time interval between the making of the aneurysm and angiography (p = 0.04). Aneurysmal patency was observed in 10 swines (83%). Wound infection occurred in 2 animals (16.6%) both with early onset 3 days after making of the aneurysm. After histological analysis of aneurysms, thrombus were founded partially occluding the light aneurysm in 9 animals (75%). In these animals it was observed that in average 9% of the aneurysmal lumen was filled with thrombus. Conclusion: The stable experimental model of carotid artey saccular aneurysm in swine using the internal jugular vein was developed.

Percutaneous dilatational tracheostomy (PDT) has become an appropriate alternative to conventional surgical tracheostomy. It is now performed worldwide by a diverse array of physician specialists. Although adverse events are relatively uncommon, serious complications can arise from this bedside procedure. We report a patient who suffered life-threatening hemorrhage from a common carotid artery laceration and pseudo-aneurysm formation in the innominate artery following an elective PDT procedure.

Pre-eclampsia is associated with increased risk of cardiovascular disease (CVD) later in life. The ‘gold standard’ for estimating cardiovascular risk - ultrasound assessment of the common carotid artery intima-media thickness (CCA-IMT) - does not convincingly demonstrate this increased risk. The aim of this thesis was to examine whether high-frequency (22 MHz) ultrasound assessment of the individual CCA intima and media layers and calculation of the intima/media (I/M) ratio - can indicate the increased cardiovascular risk after pre-eclampsia. After validation of the method in premenopausal women with systemic lupus erythematosus (SLE) who have a recognized increased risk of CVD, women during and after normal and preeclamptic pregnancies were investigated. Assessment of the individual artery wall layers reliably demonstrated the increased cardiovascular risk in premenopausal women with SLE, while CCA-IMT did not. The artery wall layer dimensions in women with SLE were comparable to those of postmenopausal women without SLE and were 30 years older. Among the women with normal pregnancies negative changes to the artery wall later on in the pregnancy were seen in those with lower serum estradiol, older age, higher body mass index or higher blood pressure early in the pregnancy. About one year postpartum, both the mean intima thickness and the I/M ratio had improved, compared to values during pregnancy. These findings support the theory that normal pregnancy is a stress on the vascular system. Women who developed pre-eclampsia (mean age 31 years) had thicker intima layers, thinner media layers and higher I/M ratios, both at diagnosis and one year postpartum, than women with normal pregnancies, indicating increased cardiovascular risk. Women with a history of severe pre-eclampsia (mean age 44 years; mean 11 years since the last delivery) had thicker intima layers and higher I/M ratios than women with a history of normal pregnancies, indicating long-standing negative vascular effects. Assessment of individual CCA wall layers, but not of CCA-IMT, provided clear evidence of the well-known increased cardiovascular risk in women with SLE or pre-eclampsia. The method has the potential to become an important tool in reducing cardiovascular morbidity and mortality in these women through early diagnosis and intervention.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Stroke is the third leading cause of death in South Africa, killing about 240 people a day and leaving survivors with residual disabilities. There is no clinically approved neuroprotective agent for stroke at the moment but the consumption of plant polyphenols has been suggested to offer neuroprotection against stroke and other neurodegenerative diseases. In this study, we investigated the effects of long term consumption of fermented rooibos herbal tea (FRHT) on ischemia reperfusion brain injury (I-RBI) in rats. Male adult Wistar rats were fed FRHT ad libitum for 7 weeks prior to the induction of ischemic injury by the transient bilateral occlusion of the common carotid arteries (BCCAO) for 20 minutes followed by 24 hours, 4 and 7 days of reperfusion respectively. Rats were then evaluated for neurologic deficits before sacrifice and brains harvested for assessment of brain oedema, blood-brain-barrier (BBB) integrity through Evans blue extravasation (EBE), immunohistochemical studies of apoptosis and lipid peroxidation. Oxygen radical antioxidant capacity and ferric reducing antioxidant power assays were also conducted to assess total antioxidant capacity after ischemia-reperfusion injury. Notably, the long term consumption of fermented rooibos herbal tea prevented brain oedema by reducing cerebral swelling induced by I-RBI. We also observed that fermented rooibos herbal tea offered neuroprotection against damage to the BBB and delayed neuronal death associated with BCCAO as fewer apoptotic cells were identified 7 days post BCCAO reperfusion. Significantly reduced levels of lipid peroxidation and increased levels of total antioxidant capacity were also observed in brain specimens of rats treated with FRHT. Rats treated with FRHT also showed improved neurologic outcomes when compared with the untreated animals. Our results show that FRHT has potent antioxidant and anti-inflammatory properties which can provide neuroprotective effects against neuronal cell loss, cerebral swelling, BBB disruption, lipid peroxidation and neurologic deficits following I-RBI. The use of FRHT is therefore highly recommended for patients with conditions that predispose them to stroke.

Cerebral ischemia leading to an ischemic stroke is a possible complication of a transcatheter aortic valve replacement (TAVR) procedure. This is because embolic debris can become dislodged and travel through the aortic arch, where they either continue to the descending aorta and join the systemic circulation or travel into the cerebral vasculature through the three daughter vessels that branch off the top of the aortic arch. These three vessels are the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. These three vessels lead either directly or indirectly to the cerebral vasculature, where the diameter of vessels become very small. If a large enough embolus travels into the cerebral vasculature, it can become stuck in the small cerebral vessels, blocking blood flow and cutting off the supply of oxygen to brain cells. The purpose of this study is to expand upon previous work in order to 1) create a more accurate physics simulation of blood and debris flow through the aortic arch 2) report on embolic debris distribution through the aortic arch and 3) analysis on which physical parameters affect embolic debris distribution. The physical parameters analyzed were particle diameter and particle density. This study was performed by creating a finite element model in COMSOL Multiphysics™ using a SolidWorks model of an aortic arch, with dimensions taken from a patient’s CT scan. Computational fluid dynamics was performed using a pulsatile pressure waveform throughout the aortic arch with a non-constant viscosity model. Once the velocity profile through the aortic arch matched with value ranges from literature, the particle tracing study was implemented. Both a pulsatile pressure waveform and a constant pressure model were analyzed, as well as a constant viscosity model and a non-constant viscosity model. The pulsatile pressure waveform influenced particle distribution and is recommended for future studies since this model leads to pulsatile flow, which is representative of flow through the aorta. It was seen that the non-constant viscosity model did not have a large effect on the velocity profile, but more than doubled the surface average value of viscosity. It also had an effect on the particle distribution through the aortic arch. Small diameter emboli were more likely to flow into the descending aorta, the brachiocephalic artery, and the left subclavian artery; larger emboli were more likely to flow into the left common carotid. Lower density emboli were more likely to flow into the descending aorta and the brachiocephalic artery. Averaging all densities and sizes, it was determined 44.8% of emboli flow into the three daughter vessels, but ultimately only 30.61% of emboli flow into the cerebral vasculature and have the potential to cause an ischemic stroke.

Ultraljudsundersökningar av arteria carotis communis (CCA) utförs med ultraljud vid bedömning av kärlförändringar och flödeshastigheter (FH) samt utredning av sjukdomar i CCA. Lumendiameter (LD) i CCA är en markör för riskfaktorer som leder till stroke, hjärtinfarkt och ateroskleros. Syftet med den aktuella studien är att studera om det sker någon vasoaktiv förändring i CCA vid konsumtion av koffein hos unga vuxna. Det var 33 försökspersoner som delades upp i grupper beroende på deras koffeinkonsumtionsvanor och undersöktes med ultraljud. Försökspersonerna hade innan undersökning inte konsumerat koffein på 12 timmar. Undersökningen utfördes innan konsumtion av koffeindryck och 45 minuter efter koffeinkonsumtion. En signifikant skillnad efter konsumtion av koffein påvisades i lågkonsument gruppen (grupp 1) (p.0,06) och högkonsument gruppen (grupp 3) (p=0,05). En positiv korrelation mellan LD innan och efter konsumtion (r=0,955; p <0,01) samt FH innan och efter konsumtion (r=0,393; p <0,01) av koffein kunde påvisas. Nyckelord: Carotisduplex, Kaffe, Vasoaktiv, CCA.