Ecology and acculturation among native peoples of central Brazil.

Simple exposure to Western goods may not be a sufficient explanation of why isolated village communities increase their participation in external market economies. The degree of market participation by four native villages in central Brazil is related to the difficulty of making a living from slash-and-burn subsistence agriculture as measured by the ratio of labor input to food output.

Segmental volume distensibility of the canine thoracic aorta in vivo.

Segments of the canine ascending aorta, upper descending thoracic aorta, and middle descending thoracic aorta were instrumented with ultrasonic dimension gauges and a cathetertip manometer simultaneously to measure changes in segment diameter, length, and intravascular pressure. Volume distensibility (EV) was calculated as the sum of circumferential extensibility (EC), longitudinal extensibility (EL), and high order extensibilities (EK) for each segment. The EC and EL were linear expressions that represented percentage volume changes per mmHg pulse pressure due to circumferential and longitudinal dimensional changes. The high order extensibilities (second and third order) accounted for the percentage volume changes per mmHg pulse pressure due to the interactions between circumferential and longitudinal dimensional changes. Mean(SEM) EV values from six dogs were 1.62(0.31), 0.84(0.08), and 0.62(0.08)% delta V/mmHg delta P for the ascending aorta, upper descending thoracic aorta, and middle descending thoracic aorta segments respectively. The EV, EL, and EK of the ascending aorta segment were significantly greater than those of the upper descending thoracic aorta and middle descending thoracic aorta segments, whereas EC was significantly less in the ascending aorta than in both the upper descending thoracic aorta and middle descending thoracic aorta segments. It is concluded that there are regional differences in aortic distensibility and its components in vivo. Longitudinal wall motion is an important determinant of these aortic mechanical properties.

Hot film coronary artery velocity measurements in horses.

Coronary velocity measurements have been carried out in anaesthetized, open-chest horses using a constant-temperature, hot-film anemometer system. L-shaped needle probes inserted by direct vessel puncture have been used to measure velocity profiles in the left common, left anterior descending (LAD), and left circumflex coronary arteries. The flow conditions were characterized by peak Reynolds numbers from approximately 200 to 1500 and values of the unsteadiness parameter from 3 to 10. These measurements indicate that in the left common coronary artery the profile is in general skewed towards the outer wall as would be expected for fully viscous flow in a curved tube. In the left anterior descending and left circumflex coronary arteries just distal to the bifurcation, the skewing was found in general to be away from the flow divider. However, in regions of the LAD and left circumflex 5-6 diameters downstream of the bifurcation, the peak systolic and diastolic profiles were indicative of a more fully developed, Poiseuille type flow with only slight skewing observed. The results of this study indicate that the flow in the coronary system, though in general laminar and disturbance free, is extremely varied in character and may exhibit large amplitude, low frequency flow oscillations. Furthermore, for these vessels which all lie on the surface of the myocardium, large systolic flows were observed to be present, even though the major portion of the volume flow was reserved for the diastolic period.

Neuropathology of mitral valve prolapse in man and cardiopulmonary bypass (CPB) surgery in adolescent Yorkshire pigs.

We investigated the brains of non-demented individuals with mitral valve prolapse (MVP) and found evidence of Alzheimer-like lesions. This neuropathology consisted of premature presence of beta-amyloid-containing senile plaques (SP) without increased prevalence of neurofibrillary tangles. Low levels of SP occurred in 20 to 45- year-old subjects with MVP, and much greater densities were observed in subjects between 45 and 62 years of age. We also investigated the brains of adolescent Yorkshire pigs undergoing cardiopulmonary bypass surgery and likewise found evidence of Alzheimer-like neuropathology. This took the form of intraneuronal accumulation of beta-amyloid immunoreactivity and increasing numbers of Alz-50 immunoreactive neurons with reduced recovery of cardiac efficiency after the surgery. Based on prevailing concepts in Alzheimer's disease, it is feasible to hypothesize that cognitive dysfunction occurring after cardiopulmonary bypass surgery with coronary artery grafting or valve repair/replacement is a functional sequela of AD-like neuropathology. This postulate is based on the premise that an individual seeking such surgery would have pre-existing, elevated AD-like neuropathology to start with. It is further coupled with the probability that these forms of cardiovascular surgery exacerbate the extent and progression of AD-like neuropathology.

Geometry and pump function in cardiac ventricular hypertrophy.

Ventricular pump function can be quantified by the inverse relation between pressure and output, i.e., the pump function graph, which is obtained by varying arterial load without changing end-diastolic volume, inotropic state and heart rate. The ratio of pressure and output, i.e., the peripheral resistance, can be represented in the same graph by a line through the origin. The 2 pressure-output relations intersect in the working point, i.e., the pressure and flow at the prevailing steady state. In normal, anesthetized cats the ventricle appears to be matched to the arterial load in the sense that the working point is found at the optimal power, i.e., the optimal value of the product of pressure and output along the pump function graph. To maintain this matching criterion during pressure overload, the ventricular volume has to remain the same while thickening of the wall takes place: concentric hypertrophy. With volume overload, matching would be preserved with eccentric hypertrophy. Because volume and pressure overloads typically lead to eccentric and concentric hypertrophy, respectively, the matching criterion may be a valuable predictor of the geometric changes found with changes in load. This idea was further investigated experimentally by determining the position of the working point in the perinephritic cat that had 1 kidney removed and the other wrapped in cellophane for 15 to 26 weeks. The working point was no longer found at the optimal power, indicating that either matching was permanently comprised or that the ventricle was still trying to restore matching.

Early endotoxic shock results in enhanced vasodilator responses to nitroglycerin but unaltered responses to neuropeptides calcitonin gene-related peptide and substance P.

To determine the role that vasoactive neuropeptides, calcitonin gene-related peptide, and substance P play in tissue-blood flow regulation during early septic shock, we examined the responsiveness of arteries removed from pigs 3 h after administration of Escherichia coli lipopolysaccharide or saline vehicle. The carotid, cranial mesenteric, and left anterior descending coronary arteries were excised, and rings were cut from each vessel. Constrictor responses were obtained to cumulative doses of norepinephrine or potassium chloride. Rings were reconstricted and challenged with acetylcholine, substance P, calcitonin gene-related peptide, and nitroglycerin. Lipopolysaccharide significantly increased the cranial mesenteric artery's response to high concentrations of norepinephrine and the response to nitroglycerin in all vessels. This enhancement of responses to nitroglycerin suggests augmented smooth-muscle responsiveness to an exogenous source of nitric oxide, possibly associated with early depression of basal endothelial function. Depression of agonist-induced nitric oxide release may mask such enhancement with endothelial-dependent dilators and may enhance the response to adrenergic constrictors in some vascular beds.

Preincubation of endotoxin with monoclonal anti-lipid A (E5), but not in vivo treatment, inhibits circulatory dysfunction.

Monoclonal antibodies (mAb) directed against the toxic lipid A portion of lipopolysaccharide (LPS) have been shown to bind lipid A in vitro, but clinical trials of such mAbs have yielded mixed results. In 53 rats instrumented for macrocirculatory and cremaster muscle microcirculatory measurements, we examined whether E5, a murine-derived anti-lipid A mAb, could inhibit LPS-induced circulatory dysfunction when incubated with LPS in vitro or given separately in vivo prior to LPS administration. Compared with Control rats (Group I), rats infused with 10 mg/kg Escherichia coli LPS (Group II) displayed marked decreases in arterial pressure and cardiac output and marked decreases in erythrocyte velocity in second, third, and fourth order skeletal muscle arterioles. Infusion of 2 mg/kg E5 90 min prior to LPS infusion (Group III) did not improve cardiovascular performance. In contrast, incubation of LPS with either 2 mg/kg (Group IV) or 10 mg/kg (Group V) E5 prior to infusion significantly attenuated LPS-induced changes in both macrocirculatory and microcirculatory function. Further investigation of the disparity between the in vitro and in vivo neutralizing capacity of anti-lipid A mAbs may aid interpretation of the variable clinical results achieved with these preparations.

Link between heart disease, cholesterol, and Alzheimer's disease: a review.

Increased prevalence of Alzheimer's disease-like beta-amyloid deposits in the neuropil and within neurons occurs in the brains of non-demented individuals with heart disease. Heart disease is a prevalent finding in Alzheimer's disease, and may be a forerunner to the dementing disorder. In the cholesterol-fed rabbit model of human coronary heart disease there is production and accumulation of beta-amyloid in the brain. This accumulation of beta-amyloid can be reversed by removing cholesterol from the rabbits' diet. In culture cells, a cholesterol challenge has been shown to increase production of beta-amyloid, and dramatic reductions of cholesterol produced by HMG Co-A reductase inhibitors decrease production of beta-amyloid. Increased beta-amyloid production is also produced by dietary cholesterol in a number of transgenic mouse models of Alzheimer's disease. Administration of HMG Co-A reductase inhibitors may block beta-amyloid production caused by dietary cholesterol in rabbits. Clinical trials testing the benefit of HMG Co-A reductase inhibitors in the treatment of Alzheimer's disease are underway.

Skeletal muscle microcirculatory response to rat alpha-calcitonin gene-related peptide.

We used in vivo video microscopy to determine the effect of increasing doses of rat alpha-calcitonin gene-related peptide (rCGRP) on rat cremaster muscle arterioles in the presence or absence of the nitric oxide synthase inhibitor N-omega-nitro-L-arginine (L-NNA). Male Sprague-Dawley rats (118-148 g) were anaesthetized with pentobarbital, and neurovascularly intact cremaster muscles were imaged. Changes in the diameter, erythrocyte velocity and volume flow in second-(A2), third-(A3), and fourth-(A4) order arterioles were determined. To produce uniform arteriolar tone, the cremaster preparation was challenged with norepinephrine (NE: 10(-7) M). L-NNA (10(-4) M), which was shown to inhibit acetylcholine-(ACh: 10(-6) M) induced arteriolar dilations, was added to 16 of the preparations. Preparations were then challenged by adding cumulative log concentrations of rCGRP (10(-12)-10-7) M; n = 16) or an equivalent volume of vehicle (n = 19) to the bath. Following rCGRP challenge, arterioles were maximally dilated with 10(-5) M nitroprusside (NP). rCGRP caused significant dose-dependent increases in erythrocyte velocity and volume flow in A2 arterioles, and in diameter, velocity, and volume flow in A3 and A4 arterioles, by 10(-8) M, when compared with vehicle-treated controls. L-NNA had no significant effect on rCGRP-induced responses. These data indicate that rCGRP causes dose-dependent dilation of skeletal muscle resistance arterioles at a concentration similar to that observed in larger vessels. This dilation does not appear to be dependent on the vascular production of nitric oxide from L-arginine.

Coronary vascular and myocardial effects of substance P in hypercholesterolemic rabbits.

Age-matched male New Zealand white rabbits (n = 16) were allocated to two groups: group 1 (n = 8) received a standard rabbit diet; group 2 (n = 8) received a 2% cholesterol-enriched diet. After 8 weeks of prescribed diet, hearts were excised and placed on a constant perfusion pressure Langendorff-type apparatus. Coronary flow, left ventricular pressure, and isovolumic dP/dt were continuously measured. Baseline recordings were made and then a single 5 nmol bolus dose of substance P was delivered into the coronary perfusate. Mean serum cholesterol levels in group 1 were 53 +/- 17 (SEM) mg.dl-1, in group 2 1438 +/- 143 mg.dl-1. In group 1, the injection of substance P caused mean coronary flow to increase 39 +/- 6%, mean coronary vascular resistance to decrease 28 +/- 3%, and mean dP/dt to increase 11 +/- 4%. In group 2, coronary flow increased 57 +/- 13%, coronary vascular resistance decreased 33 +/- 5%, and dP/dt increased 17 +/- 4%. Within groups, values changed significantly from baseline but these changes were not significantly different between groups. The duration of coronary flow response was 113 +/- 20 s in group 1 and 63 +/- 8 s in group 2. Substance P is a potent dilator of coronary resistance vessels and has positive inotropic effects in the rabbit. High levels of cholesterol exposure do not alter the magnitude of substance P-induced vasodilation, but the duration of the response is shortened.

Substance P induces biphasic endothelium-dependent relaxations in pig and rabbit carotid arteries.

Careful handling and preparation of freshly harvested vessels from 22 pigs and 12 rabbits revealed a two-phase vasorelaxation response to cumulative doses of substance P (SP). A rapid, transient relaxation was observed during the cumulative dose-response and a new plateau of equilibrium was seen following an increase in developed force after the last dose of SP. The phase 2 response is also produced by submaximal doses of SP and is not altered by pretreatment of the rings with Indomethacin. Acetylcholine (ACh) caused an endothelium-dependent relaxation but without evidence of a phase 2 plateau. N omega-Nitro-L-Arginine (L-NNA) and N omega-Nitro-L-Arginine Methylester (L-NAME) pretreatment resulted in a shift to the right in the phase 1 response to SP and a complete blockade of phase 2. Methylene blue caused nearly complete block of both phases. Nitroglycerin caused a dose-dependent and prolonged vasorelaxation with no phase 2.

Development of a minimally invasive technique for coronary revascularization in a porcine model.

BACKGROUND: This porcine model was designed to develop a minimally invasive method for internal mammary artery (IMA) grafting using an anterior mediastinal approach and without routine use of cardiopulmonary bypass. METHODS: Assessment was made of IMA mobilization through a small parasternal incision, the feasibility of coronary artery grafting with cardiopulmonary bypass using this approach, and conditions for off-pump bypass grafting. RESULTS: In group 1, 6 pigs underwent IMA mobilization through a 5-cm horizontal midparasternal incision. Of the 2 group 2 pigs, 1 underwent IMA grafting to the left anterior descending coronary artery and the other, bilateral IMA grafting to the left anterior descending and right coronary arteries using femoral-vessel cardiopulmonary bypass. In group 3, 4 of 10 pigs had successful off-pump grafting during retrograde regional coronary venous perfusion of arterial blood. Retrograde coronary venous perfusion could not be established in the other 6 pigs, and attempts at off-pump grafting failed. CONCLUSIONS: The study demonstrates that coronary artery grafting with the IMA by this minimally invasive off-pump method is feasible, although it draws attention to areas of concern and potential methods of correction. The model provides a realistic and important learning platform for the surgical issues involved with this minimally invasive technique.

Increased density of cortical apolipoprotein E immunoreactive neurons in rabbit brain after dietary administration of cholesterol.

Rabbits were fed 2% cholesterol diet for 4, 6 and 8 weeks or control diet for 6 weeks. Frontal cortex and hippocampal formation were stained with apolipoprotein E (Apo-E) antibody using standard immunocytochemical methods. The number of neurons expressing the Apo-E epitope and the intensity of Apo-E immunoreactivity increased with increasing time on the cholesterol diet. Because Apo-E chaperones cholesterol in the brain, the data may suggest that elevated circulating levels of cholesterol eventually cause increased cerebral levels.

Three-dimensional tissue deformation in subcutaneous tissues overlying bony prominences may help to explain external load transfer to the interstitium.

Anesthetized, carefully positioned, female, weanling, white-haired pigs were used to test the hypothesis that (1) interface pressure, the pressure between the skin and an external load, can be used to predict the interstitial fluid pressure over the wings of ilia and the last dorsal spinous process and (2) three-dimensional tissue deformation of the interstitium under the load could partially explain how the external load is transferred at that site. When a 4 or 8 kg load was distributed over the hips of the pigs, the interface pressures over the ilia were approximately 145 and 207 cm H2O, respectively. Approximately 28% of this pressure was transferred to the tissue, resulting in an increase in interstitial fluid pressure of approximately 39 cm H2O for the 4 kg load and 60 cm H2O for the 8 kg load. However, over the spinous process, about 42-43% of the load was transferred to the interstitium. Subcutaneous tissue marker movement occurred along the gamma and theta spherical coordinate but no significant tissue marker movement along the phi coordinate. The latter indicates no significant twisting of the tissue while the former demonstrates three-dimensional shearing. There were also indications of tissue creep since the markers continued to move with constant loading.

Contribution of the lung to total body clearance of meperidine in the dog.

The potential role of the lung in the disposition of meperidine was examined in six conscious dogs instrumented for measurement of appropriate hemodynamic parameters. Following an intravenous bolus injection of 5 mg/kg, blood samples were collected simultaneously from cannulas placed in the left ventricle and the pulmonary artery, concurrent with the hemodynamic measurements. Pulmonary clearance, calculated from concentration differences between pulmonary arterial and left ventricular blood and pulmonary blood flow, averaged 12.1 +/- 3.70 mL/min/kg, accounting for 58 +/- 13% of the total clearance of the drug. These results help resolve differences between previously reported meperidine clearance in the dog and physiological blood flows and imply that the dog may be a poor model for this drug in humans where clearance is primarily hepatic.

Effects of internal mammary artery pedicle coronary artery bypass grafting on aortic valve leaflet positioning.

Approximately 50% of all patients who require replacement of the aortic valve (AVR) also require coronary artery bypass grafting (CABG) for concomitant coronary artery disease. Internal mammary artery (IMA) pedicle grafts are being used with increasing frequency for this purpose. Since the ostia of the IMA are considerably downstream from the sinus of Valsalva we hypothesized the CABG would change the local coronary flow dynamics and possibly alter the timing of both natural and prosthetic valve opening and closing dynamics. Both IMA'S were dissected as pedicle grafts in five pigs and the animals were put on cardiopulmonary bypass. Anastomotic sites were the proximal 1/3 of the left anterior descending and proximal 1/5 of the right coronary arteries. Aortic root, left ventricular and right ventricular pressures were measured and flowmeter transducers were placed on the aortic root, the left main coronary artery, the right coronary artery, the left IMA and the right IMA for measuring flows. Echocardiographic images of the aortic valve, in the longitudinal view, were recorded with a simultaneous ECG. Time points were defined during each cardiac cycle based upon characteristic points in the native coronary hemodynamics. These were identified at 8, 14 and 22% of the cycle (valve opening) and 38, 45 and 55% of the cycle (valve closing). Calculations were made based upon each cycle being initiated with the ECG R wave peak. Significant alterations in flow patterns were identified and quantitated between native coronary and IMA grafts. Only minor changes in valve positioning were identified. These differences in natural valve leaflet position occurred at 22% and 45% of the cycle.

Thrombogenicity of polyethylene oxide-bonded Dacron sewing ring in a mechanical heart valve.

BACKGROUND AND AIM OF THE STUDY: The aim of the study was to evaluate the effect of binding hydrophilic polyethylene oxide (PEO) onto Dacron fibers in the sewing ring of a mechanical heart valve (MHV), in terms of thrombogenicity of the prosthesis. METHODS: The study was performed in blinded fashion. Six Yorkshire-cross pigs (bodyweight 35-45 kg) were implanted with MHVs, in the mitral annulus, with the PEO-treated sewing ring. An additional five pigs implanted with identical MHVs, but with untreated sewing rings, served as controls. PEO of chain-length 10,000 Da was grafted to Dacron fibers using gamma irradiation. PEO-bonded Dacron fibers (diameter 100 microns) were used to weave the sewing ring, which was then assembled on a titanium stent (OD 25 mm). Autologous platelets were labeled with 111In-tropolone and injected intravenously (850-1250 microCi per injection) into the pigs on removal from cardiopulmonary bypass (CPB). At 20-24 h after surgery, platelet thrombi adherent to MHV components, and shed emboli trapped in the brain, lung, heart, kidneys and other organs/connective tissues were imaged using a gamma camera. The animals were killed and the amounts of thrombi adherent to MHV components and organ-trapped emboli quantified using an ionization chamber and gamma counter. RESULTS: There was no statistically significant difference in the adhesion of 111In-labeled platelets to either control sewing rings (0.08 +/- 0.06% dose) or PEO-treated rings (0.19 +/- 0.21% dose). The thrombogenicity of MHV components in both animal groups was in the ascending order: Dacron ring > Teflon pledgets > polypropylene sutures > titanium housing > pyrolytic carbon. The number of platelet-emboli trapped in the organs was not significantly different between the two groups. CONCLUSIONS: Simple modifications may not reduce platelet thrombosis or wound-healing of the sewing ring in the acute phase, at which time several complex processes are activating and inactivating platelets and coagulant factors during CPB and implantation of MHVs.

A search for ultrasonic cavitation within the canine cardiovascular system.

Resonant bubble detectors (RBD) were used to search for both pre-existing bubbles and bubbles created by cavitation within the cardiovascular system of 22 dogs. No pre-existing bubbles of 3.8 micron diam or larger were found, nor were any created by exposing the left ventricle to 0.51-1.61 MHz ultrasound of up to 16 W/cm2 spatial-peak intensity. Bubbles introduced into the arterial system by high speed injection were readily detected and could be held in the heart by 1 MHz ultrasound at 1-2 W/cm2 or above. A surprising observation was that gas bubbles of resonant size injected into the left ventricle and held by ultrasound did not multiply continuously as happens in saline or water in vitro. This in vivo system was designed to assess the potential for cavitation bioeffects and the essentially negative results obtained may limit the expected or potential risk of this mechanism in regard to medical applications of ultrasound.

Haemolysis in vivo by therapeutic intensities of ultrasound.

Therapeutic intensities of MHz ultrasound directed at the upper abdominal area of rats in vivo resulted in damage to the circulating red blood cells. This damage was detected as free haemoglobin in the plasma as well as microspheres and spherocytic cell fragments which are characteristically produced when blood is heated to more than 49 degrees C. The magnitude of this effect increased with increasing frequency of the ultrasound and was dependent upon the time-averaged intensity, even when the ultrasound was delivered as bursts of high spatial peak intensities. Thermal lesions were found above 10 W/cm2 SP at 1 MHz and above 3 W/cm2 SP at 3.4 MHz. These results show that the observed blood cell damage is primarily a thermal effect which occurs as the blood perfuses anatomical structures which are being heated by the ultrasound beam.

On-line pressure estimation for a left heart assist device.

Long term measurement of blood pressures is essential for control of circulatory systems with artificial hearts or circulatory assist devices. Efforts to obtain reliable continuous direct measurements of blood pressures, however, have not been successful. This paper describes an on-line pressure estimation technique for use with a portable pneumatically driven left heart assist device. The on-line maximum likelihood algorithms are used for the estimation with the technique based on the use of physical models of the components of the driver and blood pump system. This technique estimates the inlet and outlet pressures of the blood pump. The directly measured driving air pressure and piston position of the pneumatic actuator are used for the estimation. In vitro and in vivo experiments were made to test the use of the on-line estimation technique. The results show successful linear correlations between the actual pressures and their estimates. This technique offers the following advantages: accurate pressure information for on-line control, accessibility to the transducers for recalibration, and noninvasive location of the transducers.