Simulating blood flow in microvessels is a major challenge because of the numerous blood cells suspended in the blood. Furthermore, red blood cells (RBCs), which constitute 45% of the total blood volume, are highly deformable. RBCs deformation and RBC-RBC interactions determine the complex rheology of the blood. In this research, we simulate the blood flow in periodic two dimensional channels and conduct numerical experiments on the cell-free layer which appears near the wall. We use the boundary integral method and the smooth particle mesh Ewald method to represent the blood flow, and cells are modeled as deformable capsules. In the numerical experiments, we examine four possible mechanisms that may contribute to the cell-free layer: RBC deformation, RBC aggregation, configuration constraint, and the lubrication mechanism. Our simulations correctly represent hemodynamic phenomena such as the blunt velocity profile and the Fåhræus effect. We observed that more deformable RBCs migrate more away from the wall, and, consequently, the thickness of the cell-free layer increases. However, RBC aggregation increased the cell-free layer thickness by only 5%. In the experiment on the configuration constraint, no cell-free "layer" was detected when we removed cells which intersected an artificial constraint in the microvessel. In the last experiment on the lubrication mechanism, the cell-free layer disappeared at a no-shear stress boundary, and the hematocrit profile was similar to that in the constraint test. Therefore, this research clearly shows that the cell-free layer is generated by the lateral migration of deformable RBCs due to the lubrication mechanism. / text

Proper distribution of blood flow in the microcirculation is necessary to match changing oxygen demands in various tissues. How this coordination of perfusion and consumption occurs in heterogeneous microvascular networks remains incompletely understood. Theoretical models are powerful tools that can help bridge this knowledge gap by simulating a range of conditions difficult to obtain experimentally. Here, an algorithm is first developed to estimate blood flow rates in large microvascular networks. Then, a theoretical model is presented for metabolic blood flow regulation in a realistic heterogeneous network structure, derived from experimental results from hamster cremaster muscle in control and dilated states. The model is based on modulation of arteriolar diameters according to the length-tension characteristics of vascular smooth muscle. Responses of smooth muscle cell tone to myogenic, shear-dependent, and metabolic stimuli are included. Blood flow is simulated including unequal hematocrit partition at diverging vessel bifurcations. Convective and diffusive oxygen transport in the network is simulated, and oxygen-dependent metabolic signals are assumed to be conducted upstream from distal vessels to arterioles. Simulations are carried out over a range of tissue oxygen demand. With increasing demand, arterioles dilate, blood flow increases, and the numbers of flowing arterioles and capillaries, as defined by red-blood-cell flux above a small threshold value, increase. Unequal hematocrit partition at diverging bifurcations contributes to capillary recruitment and enhances tissue oxygenation. The results imply that microvessel recruitment can occur as a consequence of local control of arteriolar tone. The effectiveness of red-blood-cell-dependent and independent mechanisms for the metabolic response of local blood flow regulation is examined over a range of tissue oxygen demands. Model results suggest that although a red-blood-cell-independent mechanism is most effective in increasing flow and preventing hypoxia, the addition of a red-blood-cell-dependent mechanism leads to a higher median tissue oxygen level, indicating distinct roles for the two mechanisms. In summary, flow rates in large microvessel networks can be estimated with the proposed algorithm, and the theoretical model for flow regulation predicts a mechanism for capillary recruitment, as well as roles for red-blood-cell-dependent and independent mechanisms in the metabolic regulation of blood flow in heterogeneous microvascular networks.

Changes in cerebrovascular reactivity (CVR) to carbon dioxide (CO2) are reported in many neurological conditions. My aim was to validate a method for computerized prospective targeting of CO2 levels (RespiractTM) as a bedside tool for impaired CVR. I hypothesized that 1) The RespiractTM and TCD method can be used to detect impairment of CVR after SAH and that 2) CVR is impaired in SAH patients. In 18 SAH patients and 26 controls CVR index was calculated dividing the percentage change in middle cerebral artery blood flow velocity (MCAv) by the change in PETCO2. The absolute MCAv values were similar in both groups, but CVR was significantly different (hypercapnia: 0.044 ± 0.076 - controls; 0.014 ± 0.037 - SAH; p=0.0007). I showed that impaired CVR can be detected at the bedside using TCD and CO2 challenge with the RespiractTM, control of CO2 is precise and minimal changes are required.

Changes in cerebrovascular reactivity (CVR) to carbon dioxide (CO2) are reported in many neurological conditions. My aim was to validate a method for computerized prospective targeting of CO2 levels (RespiractTM) as a bedside tool for impaired CVR. I hypothesized that 1) The RespiractTM and TCD method can be used to detect impairment of CVR after SAH and that 2) CVR is impaired in SAH patients. In 18 SAH patients and 26 controls CVR index was calculated dividing the percentage change in middle cerebral artery blood flow velocity (MCAv) by the change in PETCO2. The absolute MCAv values were similar in both groups, but CVR was significantly different (hypercapnia: 0.044 ± 0.076 - controls; 0.014 ± 0.037 - SAH; p=0.0007). I showed that impaired CVR can be detected at the bedside using TCD and CO2 challenge with the RespiractTM, control of CO2 is precise and minimal changes are required.

Cerebral blood flow dynamics is an essential component for preserving cerebral integrity. Cerebral blood flow abnormalities are often seen in patients with central nervous system pathologies such as epilepsy, migraine, Alzheimer's Disease, vascular dementia, stroke, and even HIV/AIDS. There is increasing clinical and experimental evidence implicating cerebral hypoperfusion during ageing. The determination of cerebral perfusion has therefore become an important objective in physiological, pathological, pharmacological, and clinical investigations. The knowledge of regional cerebral blood flow further provides useful diagnostic information and/or data for a better understanding of the complex clinical presentations in patients with neurological and psychiatric disorders. Several cerebrovasoactive drugs have found application in the clinical setting of cerebrovascular diseases such as migraine and dementia. Due to the similarities between humans and non-human primates with respect to their brains, both structurally and behaviourally, numerous studies have been conducted and several non-human primate models have been developed for physiological, pathological, pharmacological, and clinical studies, amongst others in Parkinson's disease and diabetes. The relatively large size of the Cape baboon Papio Ursinus with a weight of 27-30 kg for a large male, makes this primate especially suitable for in vivo brain studies using radiotracers and Single Photon Emission Computed Tomography (SPECT). The main aim of the current study was therefore to develop a suitable radiotracer (99m Tc-hexamethylpropylene amine oxime (HMPAO) or 99m Tc_ethyl_cysteinatedimer (ECD) or 123l-iodoamphetamine (IMP)) for adapted in vivo cerebral blood flow measurements in a non-human primate (Papio ursinus) as an investigative model. The model was to be validated and applied in various drug studies for the evaluation of pharmacological interventions. The study design made use of split-dose methodology, whereby the radiopharmaceutical (radiotracer) was administered twice during each study. The first administration was injected soon after the induction of the anaesthesia, and was followed by the first SPECT data acquisition. The second administration of the radioligand, a double dose of radioactivity with respect to the first radioligand injection, was done at a specific time during the study, which took into account the pharmacodynamics of the drug. A second SPECT data acquisition followed subsequently. The drugs that were included in the study were acetazolamide, a carbonic acid anhydrase inhibitor (often used in nuclear medicine to determine cerebral reserve); sumaptriptan, a 5-HT (serotonin) agonist used for treatment of migraine; sodium valproate (an anti-epileptic drug); nimodipine, a calcium channel blocker and nitro-glycerine, a vasodilator used for angina. Arterial blood pressures were recorded from a catheter in the femoral artery and heart rates were concurrently monitored. The split-dose method was successfully applied to develop a non-human primate cerebral blood flow model under anaesthesia. The model showed differences in cerebral perfusion of the different anaesthesia regimes. These anaesthesia data sets were suitable as control/baseline results for drug intervention studies. Acetazolamide evaluation through the split-dose method in the baboon confirmed the sensitivity of the model by presenting comparable perfusion. This result compared to those already familiar prompted the model to be applied in pharmacological intervention studies. Subsequent results of these investigations showed increases in perfusion for single drug nimodipine treatment (25%). However, nimodipine attenuated the increases in perfusion when administered in combination with acetazolamide. Sumatriptan was able to decrease and normalise the increased perfusion after long duration anaesthesia. Decreased cerebral blood flow was observed for combinations of nimodipine with sodium valproate suggesting drug-drug interaction with important clinical implications. Similar decreases were found also for sumatriptan and nitro-glycerine when administered in combination with nimodipine. Studies with the various tracers (99m Tc_HMPAO or 99m Tc_ECD or 123l_IMP) showed clear differences in the perfusion data, confirming variation in the biochemical performance of the tracers. These differences, if not taken into consideration, caution for inappropriate clinical conclusions and subsequent erroneous therapeutic decisions. Improvement of radiotracer efficacy was subsequently attempted through application of the cyclodextrine complexation approach. Although cyciodextrine technology did not markedly improve the brain disposition of the 99m Tc-ECD, protection of the tracer against degradation was demonstrated. This study encouraged further exploration of this method for protection of the tracer against chemical and metabolic degradation. The current study was aimed to develop and effectively apply a non-human primate model with nuclear medicine technology for cerebral blood flow determinations after pharmacological interventions. This was achieved through the split-dose method and dedicated computer programming, which yielded a successful model with the non-human primate under anaesthesia. The model was validated with the application of acetazolamide to confirm familiar cerebrovascular reserve results, indicating that the model is sensitive to CBF changes. The model was also effectively applied in several pharmacological intervention studies, whereby cerebropharmacodynamics of selected drugs were investigated and established. This unique model of a non-human primate, Papio ursinus for cerebral blood flow determinations has served pharmacological research successfully during the past 12 years and could do so in the future, with scope to investigate new frontiers with improved technologies. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2004.

Abnormal leukocyte adhesion (i.e. leukostasis) to retinal vascular endothelial cells occurs in early diabetes. The processes of leukostasis have been clearly demonstrated in the vascular endothelium of patients with diabetes. In non-proliferative DR, clinical outcomes are manifested by excessive permeability from inflammatory progression leading to inner blood retinal barrier disruption, endothelial cell damage and widespread capillary nonperfusion. Diabetes promotes vascular leakage in DR by upregulation of adhesion molecules. Moreover, many of the pathological changes in NPDR are related to abnormalities in retinal blood flow. Studies have shown that specific circulating markers of inflammatory activity and endothelial dysfunction are associated with clinical signs of diabetic retinopathy. However, few have found an association between circulating levels of inflammatory and endothelial dysfunctional markers and abnormal retinal hemodynamics in patients with non-proliferative DR. The specific aims of this thesis are as follows: (Chapter 3)To correlate baseline levels of inflammatory and endothelial dysfunction markers and 1) baseline retinal arteriolar hemodynamics and 2) any disturbance in retinal hemodynamics over 6-month time in terms of vessel diameter, blood velocity, maximum-to-minimum velocity ratio and volumetric flow. In Chapter 4: To correlate circulating levels of inflammatory and endothelial dysfunction markers and 1) baseline vascular reactivity and 2) any disturbance in vascular reactivity after 6-month time in terms of vessel diameter, blood velocity, maximum-to-minimum velocity ratio and volumetric flow in patients with increasing non-proliferative diabetic retinopathy (NPDR) severity. Methods for Chapter 3: Diabetes subjects were stratified into either mild-to-moderate (Group 2) or moderate-to-severe (Group 3) NPDR based on their retinopathy status. Age-matched non-diabetics were recruited as controls (Group 1). Forearm blood sample was collected to determine baseline levels of inflammatory and endothelial dysfunctional markers. At visit 1, baseline retinal hemodynamics was acquired using Canon Laser Blood Flowmeter. Patients returned for a visit 2 (6 month follow-up visit) and retinal hemodynamics was reassessed. Baseline levels of inflammatory and endothelial dysfunctional markers compared between groups and correlated with both baseline and change in retinal hemodynamic parameters over 6-month time. For Chapter 4: Diabetes subjects were stratified into either mild-to-moderate NPDR or moderate-to-severe NPDR based on their retinopathy status. Age-matched non-diabetics were recruited as controls. At visit 1, forearm blood sample was collected to determine levels of inflammatory and endothelial dysfunctional markers and baseline vascular reactivity response was acquired. Retinal blood flow data was acquired while subjects breathed air. Retinal blood flow measurements were then acquired after exposure to isocapnic hyperoxic stimuli. At visit 2 (6 month follow-up), retinal vascular reactivity was reassessed. Baseline levels of inflammatory and endothelial dysfunctional markers compared between groups and correlated with both magnitude of baseline and change in vascular reactivity in terms of retinal hemodynamics. Results of Chapter 3: Maximum-to-minimum velocity ratio (max: min) was found to be significantly elevated in the group 3 compared to group 1 at baseline (0.72 vs. 0.49, after Bonferroni correction P<0.01). Both sICAM-1 and sE-selectin were significantly elevated as a function of group (ANOVA p=0.02 and p=0.04). A post hoc Bonferroni test showed that Group 3 had significantly higher in both sICAM-1 and sE-selectin levels compared to Group 1 (234.0 vs. 151.5 ng/ml, P=0.02 and 53.4 vs. 27.6 ng/ml, P<0.01, respectively). Hemoglobin A1c was significantly elevated across the groups (ANOVA p<0.01). A post hoc Bonferroni test showed that Group 3 had significantly higher hemoglobin A1c level compared to Group 1 (7.9 vs. 5.6 % , P<0.01). There were no significant associations found between baseline markers of inflammation and baseline retinal hemodynamics across all groups. The Δ velocity was correlated with the baseline sICAM-1 (r=0.42, p=0.02) and A1c levels (r=0.37, p=0.04) in patients with NPDR. After adjustment for all other variables (A1c, hsCRP and vWF), Δ velocity, sICAM-1 and A1c were found not to be reliable predictors of baseline retinal hemodynamics. For Chapter 4: There were no significant differences in magnitude of retinal vascular reactivity in hemodynamic parameters between groups at visit 1 or visit 2. Over 6 months time, compliance was found to be significantly reduced in patients of Group 3 compared to Group 2 (-0.4 vs. 0.1, t-test p<0.01). Both sICAM-1 and sE-selectin were significantly elevated as a function of group (ANOVA p=0.02 and p<0.01). A post hoc Bonferroni test showed that Group 3 had significantly higher in both sICAM-1 and sE-selectin levels compared to Group 1 (243.4 vs. 157.3ngml, P<0.01 and 57.0 vs. 29.3 ng/ml, P<0.01, respectively). Hemoglobin A1c was significantly elevated across the groups (ANOVA p<0.01). A post hoc Bonferroni test showed that Group 3 had significantly higher hemoglobin A1c level compared to Group 1 (8.8 vs. 5.6 % , P<0.01). Baseline VR in blood velocity weakly correlates with sE-selectin (r=0.31, p=0.04) across all groups while sVCAM-1 was associated with VR in terms of blood flow (r=-0.62, p<0.01) in patients with mild-to-moderate NPDR. The ∆ blood flow after 6 months was found to be weakly associated with sE-selectin (r=0.46, p=0.03) across all groups. Finally, the ∆ blood velocity after 6 month time was found to be moderately correlated with baseline vWF Ag level (r=-0.78, p=0.02). Multiple regression analysis found that vascular inflammatory and endothelial function markers had weak predictive power for Δ hemodynamic parameters. Conclusions Chapter 3: We found weak associations between circulating markers and baseline or the disturbance in retinal hemodynamics after 6 months time. Overall, we found both an increase in rigidity of the arteriolar circulation and elevated inflammatory adhesion markers (sICAM-1 and sE-selectin) within the same population sample. Change in velocity over the follow-up period was correlated with sICAM-1 and A1c levels in patients with NPDR but the level of association was such that neither sICAM-1 nor A1c proved to reliably predict retinal hemodynamics. Finally, in Chapter 4 we demonstrated two important characteristics in early NPDR; 1) a disturbance in vascular reactivity in terms of compliance and 2) an increase in systemic markers of inflammation were found in patients with NPDR. Although systemic markers of vascular inflammation and endothelial dysfunction are not predictive of hemodynamic parameters, our study found moderate associations between baseline and disturbances in VR after 6 months time. Therefore, there is evidence that inflammation and vascular function may be related with respect to their development in NPDR.

Physical load, age and gender influence to blood pressure and maximal stresses in the pathological blood vessel palaces was studies in this work. The main research subject – pathological blood vessel and its blood flow processes that depend on physical load, pathology degree and type, age, gender and blood vessels stress characteristics. The main aim of this work – to examine blood flow characteristics, local blood pressure, stress distribution in the pathological blood vessels dependent physical load assessing blood vessels mechanical properties variations due to age, gender, blood vessel pathology type; to make simplified human efficiency evaluation methodology. The paper analyse a few main tasks: to explore physical load, blood vessels pathology degree, age and gender influence to blood pressure and tensions increase in the pathological blood vessels locations; experimentally determine blood flow rates changes in pathological blood vessels assessing; additionally investigate blood pressure and heart rate characteristics variations during set physical load and human working age range. This paper consists of introduction, four chapters, summary, literature and authors publications theses lists and two annexes. Introductory chapter discusses the test problem, work topicality, research subject, also formulates work subject and tasks, and describes research methodology, work scientific novelty, practical value of the work results, defended propositions. In the introduction end... [to full text] / Disertacijoje nagrinėjama fizinio krūvio, amžiaus bei lyties įtaka kraujo spaudimui ir didžiausiems įtempiams pažeistoje kraujagyslės vietoje. Pagrindinis tyrimo objektas – ligos pažeista kraujagyslė ir joje vykstantys kraujo tėkmės procesai, priklausantys nuo fizinio krūvio dydžio, pažeidimo laipsnio ir rūšies, amžiaus, lyties, bei šių veiksnių įtaka didžiausiems įtempiams ir spaudimui pažeistose vietose. Pagrindinis disertacijos tikslas – ištirti kraujo tėkmės charakteristikas, lokalinį kraujo spaudimą, įtempių pasiskirstymą pažeistose kraujagyslėse priklausomai nuo fizinio krūvio, įvertinant kraujagyslių mechaninių savybių pokytį dėl amžiaus, lyties, kraujagyslės pažeidimo rūšies, ir sudaryti supaprastintą darbingumo verti-nimo metodiką. Darbe sprendžiami keli uždaviniai: ištirti fizinės apkrovos dydžio, kraujagyslių pažeidimų laipsnio, amžiaus ir lyties įtaką kraujo spaudimui ir įtempių padidėjimui pažeistose kraujagyslių vietose; ekspe-rimentiniu būdu nustatyti kraujo tėkmės rodiklių pokyčius pažeistose kraujagyslėse; ištirti kraujo spaudimo ir širdies susitraukimų dažnio charakteristikų pokyčius nustatytame fizinio krūvio ir žmogaus darbingo amžiaus intervale. Disertaciją sudaro įvadas, keturi skyriai, rezultatų apibendrinimas, naudotos literatūros ir autorės publikacijų disertacijos tema sąrašai ir du priedai. Įvadiniame skyriuje aptariama tiriamoji problema, darbo aktualumas, aprašomas tyrimų objektas, formuluojamas darbo tikslas bei uždaviniai, aprašoma tyrimų... [toliau žr. visą tekstą]

BACKGROUND: Exercise is a critical treatment modality in persons with Type II Diabetes Mellitus (T2DM), however people with this disease experience chronic fatigue and a decreased exercise capacity, which affects their ability or willingness to participate in physical activity. Studies suggest that this exercise intolerance may be partly due to a reduced exercising muscle blood flow (MBF), and in particular to a reduced ability of red blood cells (RBCs) to evoke ATP-mediated vasodilation and an increase in MBF as they traverse areas of high O2 demand. Additional evidence suggests that caffeine may attenuate this impairment by enhancing the release of ATP from RBCs. HYPOTHESIS: Persons with T2DM would have reduced Forearm Blood Flow (FBF), oxygen consumption (VO2), and exercise tolerance responses to exercise compared to control (CON) subjects, and caffeine would attenuate these impairments. METHODS: T2DM (n = 4) and CON (n = 4) participants performed rhythmic forearm handgrip exercise at an intensity equivalent to 17.5 kg until “task failure” or 20 minutes of exercise was reached, after having consumed either a caffeine (5mg/kg; Caff) or placebo (Pl) capsule. FBF (Doppler and Echo ultrasound of the brachial artery), VO2 and lactate efflux (deep venous blood sampling), forearm vascular conductance (FVK), mean arterial pressure (MAP) and heart rate (HR) were quantified for each minute of exercise. RESULTS: Steady state FBF was similar across groups and treatment conditions (mean ± SE ml/min; CONCaff 553.80 ± 82.35, CONPl 583.42 ± 112.62, T2DMCaff 523.33 ± 105.39, T2DMPl 569.08 ± 134.20, NS), and this was due to similar MAP and FVK (across groups and treatment conditions, NS). VO2 and Time to Task Failure (TTF) were not different between groups and treatment conditions (NS), although TTF tended to be improved with caffeine versus placebo (10.00 ± 2.02 vs 8.24 ± 1.79 min, P=0.295). There was a strong positive relationship between FBF and TTF (r2=0.763; P=0.005). CONCLUSIONS: In the exercise model utilized, persons with T2DM do not have impaired cardiovascular responsiveness or reduced exercise tolerance, and caffeine does not provide any benefit. Differences in exercising MBF may be an underlying mechanism regarding differences in exercise tolerance. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2009-09-16 16:19:42.537

Transcutaneous oxygen pressure measurement (TCp02) using a miniaturised Clarke electrode and a heating thermistor was developed independently by Huch et al and Eberhardt et al in 1972. After its initial use to non invasively monitor arterial partial pressure (Pa02) in neonates it was proposed as a useful test of skin blood flow and possibly amputation wound healing level selection in patients with peripheral vascular disease. Unfortunately a wide range of predictive values emerged with some authors reporting amputations healing when the TCp02 value was 0 mmHg. The investigation, while still considered useful, has not gained widespread support. This study investigates the use of TCp02, establishes a value for the use of the TCp02 Index to predict amputation wound healing potential and examines the hypothesis that the use of the TcpO Index to select amputation level can reduce patient morbidity and mortality. The literature is reviewed and a series of studies evaluating TCp02 use, undertaken in the Durban Metropolitan Vascular Service Non-Invasive Laboratories, are presented. TCp02 measurements were performed in a standardised manner with the subject supine breathing room air. Measurements were taken at fixed sites, on the mid dorsum of the foot (Foot), 10 cm distal to the tibial tuberosity and 2 cm lateral to the anterior tibial margin (BKA), 10 cm proximal to the patella in the midline (AKA) and on the chest in the mid-clavicular line. A TCp02 Index, the limb to chest ratio was defined. TCp02 data derived from control subjects asymptomatic of peripheral vascular disease were shown to be similar to age matched pooled data derived from the literature. In patients with peripheral vascular disease, absolute TCp02 and the TCp02 Index were shown to fall from proximal to distal sites and again were no different to pooled data derived from the literature. Based on presenting symptoms, the fall in TCp02 and the TCp02 Index was significant from proximal to distal sites. The reduction in absolute TCp02 and the TCp02 was also related to the most distal pulse present. TCp02 values were found to be no different in patients with peripheral vascular disease with or without diabetes. When comparing TCp02 and the TCp02 Index with Doppler pressure measurements at the Popliteal artery and at the foot, and the Doppler ankle brachial index (ABI), Doppler derived data were significantly higher in diabetic patients than in non-diabetic patients. No differences were noted in TCp02 data. TCp02 was compared with the 133Xe radio-isotope skin washout test. The best correlation was (r = 0.46) was obtained with a logarithmic curve y = 10.862Ln(x) + 38.751. TCp02 was compared with antibiotic concentrations (Cefoxitin) in muscle obtained from the site of amputation and the Cefoxitin Index, the ratio of muscle antibiotic concentration to plasma concentration, as an indication of the relationship of skin TCp02 to muscle blood flow. A significant correlation was shown between the Cefoxitin Index and TCp02 (r = 0.67, p = 0.035) and the TCp02 Index (r = 0.64, P = 0.045), suggesting that skin oxygen delivery may reflect muscle antibiotic delivery and hence blood flow. TCp02 and the TCp02 Index were compared with heated and unheated laser Doppler fluxmetry (LDF) in 35 patients undergoing amputation wound healing assessment. Significant correlations were shown between heated LDF, heated LDF Index and the TCp02 Index (r = 0.63 and r = 0.69, P < 0.0001). TCp02 Index values of 0.5 and 0.55 showed an accuracy of 96.2 % in predicting amputation outcome while LDF values of 3, 4 and 5 arbitrary units gave an accuracy of 88.5 %. Using receiver operator curves, a TCp02 Index of 0.55 was shown to be the best test. Over the years 1987 and 1988, TCp02 data were gathered on 193 patients undergoing lower limb amputation for peripheral vascular disease. Information on the outcome of the amputation was available for 152 amputations. Circumstances which might result in a reduced pre-operative TCp02 reading were identified and criteria were set for the use of TCp02 to predict amputation wound healing potential. 122 amputations which met the defined entry criteria were available for evaluation. A TCp02 Index of 0.50 gave a definitive predictive value below which no amputation healed. Similarly no amputation with an absolute TCp02 of less than 27 mmHg healed. Receiver operator characteristic curves showed the TCp02 Index to be a better test than absolute TCp02. A TCp02 Index of 0.55 was shown to have the best sensitivity of96.7 %, with a specificity of79.8 % and an accuracy of 90.2 %. When introduced to clinical practice, correct use of the TCp02 Index of 0.55 resulted in a reduction in amputation revision rate from 40.3 % in 1987, to 8.2 % in 1990. Initially some surgeons felt that the TCp02 Index predicted amputation wound failure at distal sites at which healing could be expected on clinical criteria, and chose amputate at sites with a TCp02 Index value less than 0.55. These amputations failed to heal. As surgeons gained confidence in the test, they chose to follow the TCp02 data more often and the percentage of amputations performed at sites predicted by the TCp02 Index to fail , fell from 35.5 % in 1987 to 6.6 % in 1990. Over a 15 year period at King Edward VIII Hospital, the amputation revision rate has fallen from an average of 32.7 % in the first five years when Tcp02 data were not available to the surgeon, to 21.4 % and 22.9 % in the two subsequent 5 year periods when Tcp02 data were available. The mortality rates were unchanged. The decline in revision rates was less than expected and relates to the fact that approximately only 42 % of patients requiring amputation undergo the test. This is because it is time consuming and available only during weekday office hours. These studies have confirmed the usefulness of Tcp02 measurement in the non-invasive vascular laboratory. The index is shown to be superior to absolute Tcp02 as a predictive test of amputation wound healing. The introduction of several criteria to define when Tcp02 use is appropriate has refined the investigation and made it clinically useful in our setting. A Tcp02 Index of 0.55 in the appropriate patient is a useful test to predict amputation wound healing and its use has resulted in reduced patient morbidity and mortality, confirming the hypothesis tested. / Thesis (M.D.)-University of Natal, 2001.

The pattern of mucosal blood flow in normal human stomachs, and benign gastric ulcers was assesed with laser Doppler flowmetry and the relationship between a single determination of ulcer blood flow and the systemic level of growth factors was investigated. A significant ascending gradient in mucosal blood flow from the antrum to fundus was demonstrated. Different levels of cellular activity in the regions of the stomach may explain this gradient. In the gastric ulcers that healed on standard medical therapy mucosal blood flow was significantly increased in comparison to normal stomachs. In the ulcers that were refractory to standard medical therapy mucosal blood flow was significantly lower than in normal stomachs and healing ulcers. Higher systemic levels of the growth factor bFGF were demonstrated in healing ulcers compared to non-healing ulcers. Gastric mucosal blood flow can increase in response to the increased metabolic demands of healing, however impairment of this response may be an important factor preventing healing of benign gastric ulcers. It would appear that non-healing of gastric ulcers can be predicted at initial diagnosis by reduced peri-ulcer gastric mucosal blood flow and low blood levels of bFGF. / Thesis (M.Med.Sc.)-University of Natal, Durban, 1999.