Regional myocardial perfusion : experimental and clinical studies in patients with coronary artery disease

Coronary artery disease has become a world wide medical problem. There is an overwhelming association between coronary atherosclerosis, angina pectoris, acute myocardial infarction and sudden death. The narrowing of coronary arteries is thought to damage the heart by limiting appropriate changes in coronary blood flow and by causing myocardial ischemia. This thesis attempts to examine the coronary circulation in patients who present with chest pain with and without coronary artery disease. One of the aims of this thesis is to validate the use of a short-lived radionuclide to study changes in regional myocardial perfusion. This technique has been applied in clinical medicine in an attempt to describe the disturbances of regional myocardial perfusion that occur in patients with coronary artery disease. These disturbances of perfusion have been related to the patients' symptoms, the electrocardiogram and the stenosed arteries seen in the arteriogram. Krypton-81m in solution is an inert freely diffusible gas (half-life 13 seconds) which emits a single 190 kev gamma ray. This tracer, a special catheter and a gamma camera have been developed in experiments to measure changes in regional myocardial perfusion. The systematic and rand-Om errors of the method have been defined in experiments. The results show that the mixing and delivered arterial concentration of krypton-81m are stable within a useful physiological range of changes in heart rate, blood pressure and coronary blood flow. Correlations with a reference technique have shown that the method can measure changes in regional myocardial perfusion between O and 3 ml/ml/min. The invasive method, the planar imaging and the need for calibration with washout at high levels of perfusion are investigated and described as limitations that must be considered. Eighty patients presenting with chest pain have been investigated by routine clinical methods, precordial mapping of the electrocardiogram during exercise and coronary arteriography. Changes in regional myocardial perfusion at rest and during atrial pacing has been measured using krypton-81m. The results have shown that stable mixing and delivered arterial concentration of krypton-81m can be achieved in the patients. Fifteen patients with negative exercise tests all demonstrated uniform increases in regional myocardial perfusion with pacing. The remaining 65 patients with positive exercise tests and significant coronary artery disease all showed both regional increases and decreases in myocardial perfusion during atrial pacing. In 16 of the 65 patients the jeopardized segment of ventricular myocardium showed significant increases in perfusion during the first 4 to 7 minutes of pacing. Th e increase stopped and regional perfusion in the affected segment then decreased progressively until the pacing was stopped. In 23 of the 65 patients the affected segment showed no changes in perfusion for 5 to 7 minutes of atrial pacing and then showed progressive decreases in regional myocardial perfusion until the pacing was stopped. Finally, in 26 of the 65 patients the affected segment showed immediate and progressive decreases of regional myocardial perfusion starting with the commencement of atrial pacing. In all the patients with disturbed perfusion ST segment depression in the electrocardiogram appeared after (140 ± 14 sec) the regional decrease of myocardial perfusion in the affected segment. Chest pain always appeared later at 220 ± 19 sec after the appearance of disturbed myocardial perfusion. Regional myocardial perfusion returned to normal in all the patients after the atrial pacing was stopped. There was a spatial relationship between the region of the ventricles affected by disturbed perfusion and the region of the precordium showing abnormal electrocardiographic signs during the exercise test. In conclusion, this clinical study has shown that patients with chest pain who have coronary artery disease suffer decreases of regional myocardial perfusion in affected segments of the ventricles during episodes of angina pectoris induced by atrial pacing. Regional perfusion may increase, remain stable or decrease in the affected segment following the onset of a stress test such as atrial pacing. This probably represents the amount of reserve function and adaptation left in the diseased coronary circulation and may be a useful physiological indicator of the severity of coronary disease and of patients at high risk. ST segment depression and pain have a close temporal relationship to the decreases of regional myocardial perfusion that occur in these patients. These studies suggest that there is a close relationship between myocardial perfusion and metabolism in health and disease. Both myocardial perfusion and metabolism will have to be affected by any rational therapy for angina pectoris and ischemic heart disease

Mammalian Stratum Corneum Contains Physiologic Lipid Thermal Transitions

Using a new high-sensitivity differential scanning calorimeter, capable of very slow scanning rates and large sample volumes, we examined the thermal transitions in neonatal mouse stratum corneum. Both physiological and supraphysiological transitions were found in intact tissue that were displaced on cooling and obliterated by solvent treatment establishing them as lipids. Physiologic peaks were encountered in lipid extracts from the same tissues. With heating and cooling recycling we found a novel effect of thermal “fractionation” of the peaks into discrete subfractions that appeared to correspond roughly the number of bands found on thin-layer chromatography of the lipid extracts

A meta-analysis of economic diplomacy and its effect on international economic flows

This meta-analysis deals with 29 empirical studies on the trade and investment impact of economic diplomacy (embassies, consulates and other diplomatic facilities, investment and export promotion offices, trade and state visits). The meta-regression results suggest that the significance of the coefficient of economic diplomacy is more pronounced when studies use embassies as an explanatory variable as compared to studies using consulates, trade missions, state visits and export promotion agencies. If the primary dependant variable under investigation is exports one may also expect to find more significant coefficients then in an otherwise similar regression explaining the relation between economic diplomacy and imports, total trade or foreign direct investment. Furthermore empirical design factors play a role in the reported results of the studies we reviewed. Studies based on a single country will in general show lower significance

An evaluation of the Defensive Driving Course in New Zealand

The driving records of a sample of drivers ordered to complete - the Defensive Driving Course (New Zealand) by the Courts were compared with those of a sample of offending drivers, matched on age, sex and prior driving record, who did not attend the course. Twelve months before and after completion of the course, or for the comparison group, before and after the equivalent date, was the study period. Attendance at the course appeared to make, at best, no difference to the accident rate, whereas the post-treatment conviction rate was comparatively lower following the course than following the standard treatment. This finding lends support to other research in the field which shows that driver education, while having no effect on accidents, does decrease the number of post-course convictions

Large coronary arteries in humans are responsive to changing blood flow: An endothelium-dependent mechanism that fails in patients with atherosclerosis

AbstractChanges in blood flow can alter vasomotion of conduit arteries. This study examined vasomotor responses to incremental blood flow induced by papaverine in the epicardial arteries of 10 patients with angiographically normal coronary arteries (group 1) and in 14 patients with arterial irregularities (group 2) using quantitative angiography and Doppler ultrasound flow velocity measurements. An increase in coronary blood flow of 384.3 ± 32.8% (p < 0.001) in group 1 patients was associated with dilation of the proximal coronary artery segment and a 23.2 ± 4.6% increase in cross-sectional area (p < 0.001). In contrast, in group 2 patients a similar increase in coronary blood flow of 339.3 ± 18.7% (p < 0.001) was associated with mixed responses and a Modest net constriction in cross-sectional area of -7.4 ± 2.8% (p < 0.05). The dilation response to nitroglycerin was intact in group 1 (31.7 ± 4.2%, p < 0.001) and in group 2 (26.4 ± 3.2%, p < 0.001).In five patients from group 1 acetylcholine, an endothelium-dependent dilator, produced an increase in cross-sectional area of 20.7 ± 4.6% (p < 0.05) that paralleled the response to an increase in flow in the same segment (a 24.3 ± 6.1% increase in cross-sectional area, p < 0.05). Five group 21 patients demonstrated a vasoconstrictor response to acetylcholine (a − 22.8 ± 3.4% decrease in cross-sectional area, p < 0.05) together with an impaired dilation response to incremental flow (a − 6.4 ± 3.2% decrease in cross-sectional area). Thus, the normal flow-mediated dilation of coronary arteries is lost in atherosclerosis and this impairment may be due to endothelial cell vasodilator dysfunction

Calorimetric and Electron Spin Resonance Examination of Lipid Phase Transitions in Human Stratum Corneum: Molecular Basis for Normal Cohesion and Abnormal Desquamation in Recessive X-Linke Ichthyosis

Lipids appear to play a critical role as regulators of stratum corneum desquamation. In this study, we observed discrete lipid phase transitions at physiologic temperatures in both normal human scale (NHS) and in lipid extracts of NHS by differential scanning calorimetry. In contrast, such thermal transitions were not observed in recessive x-linked ichthyosis scale (RXLIS). To gain further insight into the molecular basis of the lipid phase transitions in NHS vs. RXLIS, comparable samples were evaluated by electron spin resonance, utilizing the perdeuterated probe, di-t-butyl nitroxide. Upon electron spin resonance analysis, both NHS and RXLIS demonstrated thermal phase transitions in the physiologic range; however, the nature of the lipid environments in each type varied. Whereas the environment of the spin probe was more polar in NHS than in RXLIS, the spin probe partitioned into a more “fluid” environment in RXLIS; i.e., the spin probe was more mobile in RXLIS titan in NHS lipid matrices. Because an alteration in the cholesteryl sulfate : cholesterol ratio is the primary lipid abnormality in RXLIS, model cholesterol-fatty acid-cholesteryl sulfate mixtures were prepared in proportion to the lipid composition of NHS and RXLIS. Differences were observed in both thermal transitions and in lipid microenvironments in these mixtures that paralleled those observed in scale samples. Based on these results, a model is proposed that invokes abnormal hydrogen bonding, due to increased cholesteryl sulfate, as the mechanism for the abnormal desquamation in recessive X-linked ichthyosis

Dinoflagellate blooms and physical systems in the Gulf of Maine

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution May 1990Numerous studies have shown dinoflagellate blooms to be closely related to density discontinuities and fronts in the ocean. The spatial and temporal patterns of the dinoflagellate population depend on the predominant mode of physical forcing, and its scales of variability. The present study combined field sampling of hydrographic and biological variables to examine the relationship of dinoflagellate population distributions to physical factors along the southwestern cost of the Gulf of Maine. A bloom of Ceratium longipes occurred along this coast during the month of June, 1987. A simple model which coupled along-isopycnal diffusion with the logistic growth equation suggested that the cells had a growth rate of about 0.1 d-1 , and had reached a steady horizontal across-shelf distribution within about 10 d. Fur~her variations in population density appeared to be related to fluctuations of light with periods of -10 d. To our knowledge, this was the first use of this simple diffusion model as a diagnostic tool for quantifying parameters describing the growth and movement of a specific phytoplankton population. Blooms of the toxic dinoflagellate, Alexandrium tamarense have been nearly annual features along the coasts of southern Maine, New Hampshire and Massachusetts since 1972; however the mechanisms controlling the distribution of cells and concomitant shellfish toxicity are relatively poorly understood. Analysis of field data gathered from April to September, 1987-1989, showed that in two years when toxicity was detected in the southern part of this region, A. tamarense cells were apparently transported into the study area between Portsmouth and Cape Ann, Massachusetts, in a coastally trapped buoyant plume. This plume appears to have been formed off Maine by the outflow from the Androscoggin and Kennebec Rivers. Flow rates of these rivers, hydrographic sections, and satellite images suggest that the plume had a duration of about a month, and extended alongshore for several hundred kilometers. The distribution of cells followed the position of the plume as it was influenced by wind and topography. Thus when winds were downwelling-favourable, cells were moved alongshore to the south, and were held to the coast; when winds were upwelling-favourable, the plume sometimes separated from the coast, advecting the cells offshore. The alongshore advection of toxic cells within a coastally trapped buoyant plume can explain the temporal and spatial patterns of shellfish toxicity along the coast. The general observation of a north-to-south temporal trend of toxicity is consistent with the southward advection of the plume. In 1987 when no plume was present, Alexandrium tamarense cells were scarce, and no toxicity was recorded at the southern stations. A hypothesis was formulated explaining the development and spread of toxic dinoflagellate blooms in this region. This plume-advection hypothesis included: source A. tamarense populations in the north, possibly associated with the Androscoggin and Kennebec estuaries; a relationship between toxicity patterns and river flow volume and timing of flow peaks; and a relationship between wind stresses and the distribution of low salinity water and cells. Predictions of the plume-advection hypothesis were tested with historical records of shellfish toxicity, wind speed and direction, and river flow. The predictions tested included the north-south progression of toxic outbreaks, the occurrence of a peak in river flow prior to the PSP events, the relationship of transit time of PSP toxicity along the coast with river flow volume, and the influence of surface wind stress on the timing and location of shellfish toxicity. All the predictions tested were supported by the historical records. In addition it was found that the plume-advection hypothesis explains many details of the timing and spread of shellfish toxicity, including the sporadic nature of toxic outbreaks south of Massachusetts Bay, and the apparently rare occurrence of toxicity well offshore on Nantucket Shoals and Georges Bank.This research was supported by ONR contract N00014-87-K-0007 and ONR grant N00014-89-J-111 to Donald M. Anderson, and NOAA Office of Sea Grant contract NA86AA-D-SG090

Regional variation in angioplasty practice in the United States: A report from the Hirulog angioplasty study

Pla general de la font anomenada Homenatge al poble, ubicada a la plaça Molina. A la part superior de la font, a cada costat, hi ha un escut cisellat. Sota un d'aquests es troba la frase Gratitud al Ayuntamiento.Realitzada en pedra abans de 1874