Many populations have low intakes of n-3 fatty acids, yet there is substantial evidence that the long chain n-3 fatty acid docosahexaenoic acid (DHA; 22:6n-3), found at high concentrations in the brain, is required for the proper development of the nervous system. However, less is known about requirements of long chain n-3 fatty acids for maintenance and function of the nervous system in later life. Several recent studies have reported that high amounts of long chain n-3 fatty acids reduce the extent of brain damage caused by cerebral ischemia in animals. However, whether or not a dietary deficiency of n-3 fatty acids increases the extent of injury when cerebral ischemia occurs has not been previously reported. The present studies, therefore, sought to determine if a diet deficient in n-3 fatty acids influences the extent of brain injury in the rat following cerebral ischemia. Male rats were fed an n-3 fatty acid adequate (control), an n-3 fatty acid deficient, or a high DHA diet for 5 weeks from weaning. Middle cerebral artery occlusion (MCAO) was induced and infarct volume was measured by 2,3,5,-triphenyltetrazolium chloride staining 24 hours after the procedure. Brain and platelet fatty acids were analyzed by gas liquid chromatography. DHA (22:6n-3) was 21-28% lower in brain phospholipids, and 17% lower in brain total fatty acids in the n-3 fatty acid deficient compared to control group, while 22:6n-3 was 12% higher in total brain fatty acids in the high DHA group than the control group. There was no significant difference in infarct volume (203, 220 and 218 mm³) among the control, n-3 fatty acid deficient, and high DHA groups, respectively. Platelet fatty acids and platelet aggregation were assessed to determine if these were influenced by the high DHA diet, and could possibly explain the observation of an apparent, but not statistically significant, higher number of rats with hemorrhages in the high DHA diet group. Platelet lipid arachidonic acid was not lower and platelet aggregation, assessed ex vivo using whole blood with a platelet function analyzer, was not longer in rats fed the high DHA compared to control or n-3 fatty acid deficient diets. In summary, dietary n-3 fatty acid deficiency did not increase the extent of brain injury following cerebral ischemia. The possibility that high dietary 22:6n-3 might increase susceptibility to cerebral hemorrhage will require further study.

First degree relatives (FDRs) of subjects with early onset of coronary heart disease (CHD) have higher risk of developing cardiovascular disease. We verified early CHD by angiography in the index patients and extensively phenotyped their FDRs to investigate the relationship of traditional and non-traditional cardiovascular risk factors to carotid ultrasound and coronary calcium scoring findings. B-mode carotid ultrasound was used to assess the combined intima-media thickness and plaque burden in 111 FDRs. The biochemical and anthropometrical characteristics of the FDRs were compared with those of healthy controls matched for sex, age, ethnicity and BMI. Odds ratios indicate that FDRs are more likely to have positive carotid ultrasound findings compared to controls; 2.23 (95% CI 1.14 – 4.37) for intima-media thickness and 2.3 (95% CI 1.22 - 4.35) for average total thickness. In multivariate analysis positive carotid ultrasound findings were higher in FDRs independent of age, gender, total cholesterol over HDL-c ratio, systolic blood pressure and smoking but not homocysteine which had higher values in FDRs compared to controls. In conclusion FDRs of patients with angiographically confirmed CHD have higher burden of subclinical atherosclerosis even when considered in the context of traditional risk factors. Coronary artery calcium scoring (CAC), assessed by 64-slice multi-detector computed tomography (MDCT), was used to assess burden of subclinical atherosclerosis in 57 FDRs compared to controls. FDRs have a two-fold increase in risk of having CAC positive findings; odds ratios for the 75th percentile was 1.96 (95%CI 1.04 – 3.67, p<0.05) while for the 90th percentile odds ratio was 2.59 (95% 1.232 – 5.473, p<0.05). In summary, the risk of significant CAC findings, measured by 64-slice MDCT, is two-fold higher in FDRs than controls. These findings correlate highly with carotid ultrasound findings in the same cohort. Different thresholds for CAC may be appropriate when assessing male versus female FDRs. Together increased carotid ultrasound findings and CAC scoring results in FDRs of patients with validated early onset of CHD suggest these imaging techniques as potentially useful tools in cardiovascular risk assessment that will go above and beyond the current diagnostic algorithms.

The influence of pathologies to blood pressure and velocity in blood vessels.

The influence of pathologies to blood pressure and velocity in blood vessels.

No description available.

Anxiety is a highly prevalent comorbidity in coronary artery disease (CAD) and confers increased risk of subsequent cardiac events and mortality. However, biological mechanisms of this relationship are not well understood. Ceramides are sphingolipids involved in inflammatory signaling and cell viability in the periphery and nervous system, and are implicated in pathophysiological mechanisms associated with anxiety. This study aimed to investigate relationships between plasma ceramide concentrations and anxiety symptomology as assessed by the Spielberger State-Trait Anxiety Inventory trait subscale (STAI-T) in CAD patients with linear regressions. High performance liquid chromatography coupled electrospray ionization tandem mass spectrometry was used to assay sphingolipid species. Plasma C22:0 ceramide (β=-0.232, p=0.018) concentrations and 8 other species of sphingolipids (SM18:0, SM20:1, C18:0, C20:0, C18:1, DHC22:0, LacC22:0, LacC24:1) were negatively correlated with STAI-T score when controlling for gender, BMI, and CES-D. Findings suggest specific sphingolipids to be potential markers for anxiety severity in CAD.

Erectile dysfunction and cardiovascular disease share etiologies, and commonly coexist. One unifying concept is that the arterial insufficiency in hypertension is also the primary basis for blunted sexual responses. The objective of these studies was to characterize the age-related changes in the structure and function of the pudendal artery (the main resistance vessel) in young and old normotensive and hypertensive animals in relation to erectile function. In addition, we assessed the impact of antihypertensive treatments and lifestyle modifications, such as exercise and/or caloric restriction, on erectile responses and the structure and function of the pudendal artery. In 30 week old hypertensive rats or following re-challenges at 50 and 70 weeks, antihypertensive treatment (enalapril or hydralazine) did not prevent the age-related decline in erectile function. Experiments involving cross-over kidney transplantations between treated and untreated young hypertensive rats revealed that changes in penile vasculature and not the level of arterial pressure were important for normalizing erectile responses. In addition, intervention with exercise and caloric restriction showed that these treatments substantially improved erectile responses in normotensive and hypertensive rats. The pudendal artery in young normotensive rats was found to have a thick medial layer but a relatively small lumen. With age, the pudendal lumen didn’t change, but all components of the medial layer were markedly increased. Of interest, the smooth muscle cells within the pudendal medial layer became more disorganized with aging, although iii contractions were similar. In contrast, endothelium-dependent relaxation decreased with age. Young hypertensive rats also had an increased wall thickness, but not lumen diameter or extracellular matrix. Antihypertensive therapy significantly decreased the pudendal wall thickness. In aging hypertensive rats, the pudendal artery walls were even thicker, lumen decreased and extracellular matrix greatly enhanced compared to younger rats. In addition, there were numerous regions of intimal thickening associated with marked disruptions of the internal elastic lamina. Moreover, pudendal smooth muscle cells bordering the intima and in the neointima were round in shape, and electron microscopy confirmed their synthetic state. Taken together, these findings provide key evidence of the importance of the structure and function of the pudendal artery in facilitating erectile responses. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2009-05-19 12:55:30.469

Pulmonary dysfunction following cardiopulmonary bypass surgery is a widely explored complication and a multitude of factors have been implicated, including but not limited to: operative trauma; the cardiopulmonary bypass circuit; cardioplegia; the type of donor grafts utilised; anaesthesia and fluid administered. There is a paucity of information regarding the effect of cardioplegia on the lungs. No studies have previously investigated whether allowing cold-blood cardioplegic solution to enter the lung parenchyma, during the period of cardioplegia delivery, has an effect on the clinical outcome of lung function following cardiopulmonary bypass surgery. For this reason an original study was done to determine the effect of preventing cardioplegia from entering the lungs, by evacuating overflow of cardioplegia not drained via the atriocaval cannula, by using a pulmonary artery vent. A total of 403 patients admitted to undergo full cardiopulmonary bypass were screened and 142 patients who fitted the criteria for inclusion and provided informed consent took part in this prospective double blind randomised clinical trial. The control group underwent routine cardiopulmonary bypass grafting. The study group had the intervention of a pulmonary artery vent sutured in position at the time the heart was cannulated for bypass. During cardioplegia delivery the cardioplegia was removed via the atriocaval cannula in the control group (A) and via the atriocaval cannula and the pulmonary artery vent in the study group (B). Aside from this difference, the two groups were managed identically intra- and post-operatively. Outcomes which were compared included eight time measures of arterial blood gases; electrolytes and shunt fraction; bedside lung spirometry measures over five time periods; radiographic measures of atelectasis and effusion over three time points; as well as physiotherapy and hospitalisation requirements. Numerous other potentially extraneous variables were measured and compared in order to monitor homogeneity of the study samples. The consistency of the results within each group throughout the study provides strong evidence that the measurements taken were accurate. The use of standardised equipment and vigilant adherence to the protocol ensured no extraneous deviation. The internal validity of this study was therefore good and accurate. The findings of the study however brought into question a previously accepted belief that the pulmonary artery vent prevents the overflow of cardioplegia, not drained from the right atrium, from entering the lungs. There was no literature or previous studies to confirm or dispute this accepted ‘observation’ by cardiac surgeons that the cardioplegia does enter the lung parenchyma. To therefore validate the findings of the study a further four original studies were designed and initiated. The objective of these studies was to establish the efficacy of the pulmonary artery vent and to determine whether cardioplegia indeed circulates through the lung parenchyma or merely accumulates and ‘pools’. Technetium (Tc-99m), a radio labelled isotope was added to the cold blood cardioplegia solution prior to delivery in order to determine this. In the four sub-studies it was confirmed that the pulmonary artery vent is 90-100% effective in retrieving any cardioplegic solution not drained by the atriocaval cannulae, thus confirming the effectiveness of the pulmonary artery vent in preventing cold blood cardioplegic solution from entering the lungs. The findings of the main study confirmed that respiratory impairment after uncomplicated cardiopulmonary bypass, even in low risk patients, is relatively common, as within each group there was a significant change in outcome measures over time. Inter-group comparisons however showed these changes were not significant, with both groups deteriorating by the same degree post-operatively, therefore establishing that these changes were independent of the intervention of the pulmonary artery vent. In the control group, the cold blood cardioplegia solution that did not drain from the atriocaval cannula entered the lungs and circulated the lung parenchyma during cardiopulmonary bypass. The study group made certain that none, or very little, of the cold blood cardioplegia solution entered the lungs. The main findings of this study are therefore that pulmonary function and gas exchange, although markedly reduced following cardiac surgery, are not affected by placement and suctioning via a pulmonary artery vent during the time of cardioplegia delivery intraoperatively. Furthermore, these studies strongly suggest that cold blood cardioplegia solution is innocuous to the lungs / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, 2006.

Anxiety is a highly prevalent comorbidity in coronary artery disease (CAD) and confers increased risk of subsequent cardiac events and mortality. However, biological mechanisms of this relationship are not well understood. Ceramides are sphingolipids involved in inflammatory signaling and cell viability in the periphery and nervous system, and are implicated in pathophysiological mechanisms associated with anxiety. This study aimed to investigate relationships between plasma ceramide concentrations and anxiety symptomology as assessed by the Spielberger State-Trait Anxiety Inventory trait subscale (STAI-T) in CAD patients with linear regressions. High performance liquid chromatography coupled electrospray ionization tandem mass spectrometry was used to assay sphingolipid species. Plasma C22:0 ceramide (β=-0.232, p=0.018) concentrations and 8 other species of sphingolipids (SM18:0, SM20:1, C18:0, C20:0, C18:1, DHC22:0, LacC22:0, LacC24:1) were negatively correlated with STAI-T score when controlling for gender, BMI, and CES-D. Findings suggest specific sphingolipids to be potential markers for anxiety severity in CAD.

An adjustable systemic-pulmonary artery (SPA) shunt is being developed that consists of apolytetrafluoroethylene (PTFE) graft with a screw plunger mechanism. This device would allowfull control of flow through SPA shunts used to augment pulmonary blood flow in neonates bornwith single ventricle physiology. The objective of this study is to evaluate the changes this mechanismhas on flow fields for a 4 mm and 5 mm adjustable SPA shunt. Two in vitro models wereexamined; an idealized model with an axisymmetric constriction and a model developed from 3-Dreconstruction of the actual shunt under asymmetric constriction. These models were used to measurethe instantaneous velocity and vorticity fields using Particle Image Velocimetry (PIV) underboth steady and pulsatile flow conditions. Recirculation regions and maximum values of velocity,vorticity, and shear stress are compared between the 4 mm and 5 mm models. The results indicatethat for the idealized model of both shunts, separation regions are much smaller, persistingfor approximately 0-1.75 diameters downstream of the constriction, while for the realistic modelsseparation regions of 2.5 diameters downstream were observed. Additional models of a 4 mm and5 mm shunt were tested under pulsatile conditions matching Re of 1061 and 849 and a Womersleynumber of 4.09 and 5.12, respectively, as seen in vivo. The maximum shear rates observed in bothshunts are within an allowable range without inducing platelet aggregation or hemolysis. However,regions of reverse flow exist distal to the throat, leading to possible concerns of plaque formation.Further in vivo testing will be needed to address this concern. This work is part of an extensiveeffort in developing a completely implantable adjustable systemic-pulmonary artery shunt.