The oral administration of Crotalaria spectabilis seeds to young rats induces pulmonary hypertension in them associated with right ventricular hypertrophy and an increase in the medial thickness of the pulmonary trunk and muscular pulmonary arteries. This appears to be the first direct demonstration that the oral administration of an agent may bring about pulmonary hypertension.Young rats fed on a diet which contains Crotalaria spectabilis seeds or the pyrrolizidine alkaloid monocrotaline die from congestive heart failure within 36 to 60 days. At necropsy they are found to have ascites, pleural effusions, and cardiac enlargement due to right ventricular hypertrophy (Turner and Lalich, 1965;Kay and Heath, 1966). Microscopic examination reveals an increase in the medial thickness of the pulmonary trunk (Heath and Kay, 1967) and small pulmonary arteries (Turner and Lalich, 1965 ;Kay and Heath, 1966), and in about one-third of the animals an acute necrotizing pulmonary arteritis (Lalich and Merkow, 1961;Kay and Heath, 1966). Since similar changes in the heart weight and pulmonary vasculature in man are well known to be associated with severe pulmonary hypertension (Wagenvoort, Heath, and Edwards, 1964) we thought it likely that the pulmonary vascular lesions produced in rats by Crotalaria spectabilis seeds are also associated with an elevation of the pulmonary artery pressure. It has never been shown that the oral administration of any agent can produce pulmonary hypertension, so we considered that its direct demonstration in rats fed with such seeds would be of considerable significance. Accordingly we measured right atrial and ventricular pressures in a group of rats maintained on a diet containing Cratalaria spectabilis seeds and compared these with values obtained from a group of control rats. In addition, we investigated the relation between right ventricular systolic pressure on the one hand, and the medial thickness of the small pulmonary arteries and the pulmonary trunk and the right ven-tricular weight on the other. METHODSThirteen female weanling Wistar alibino rats (initial weight 65 to 79 g.) were individually marked and divided into two groups comprising five test animals and eight controls. They were weighed at the outset of the experiment and three times weekly until its conclusion. The test animals received a diet of powdered Thomson rat cubes to which had been added finely ground Crotalaria spectabilis seeds to give a concentration of 0-1%. Control animals were given unadulterated powdered rat cubes. All animals had free access to food and water.The intracardiac pressures were determined by introducing a fine metal cannula connected to a capacitance manometer into the right jugular vein under light ether anaesthesia and advancing it along the superior vena cava into the right atrium and then into the right ventricle. It proved impossible to measure the pulmonary artery pressure directly, but for the purposes of this experiment the right ventricular systolic pressure was regarded as being equivalent ...

The objectives of this study were the development of a skeletal muscle microcirculatory preparation, in which the complications of drug anesthesia were minimized, and the quantitation of the effects of urethan and chloralose anesthesia on the microcirculation. Rats were initially anesthetized with urethan and chloralose and decerebrated by a midcollicular transection. The cremaster skeletal muscle, with intact circulation and innervation, was prepared for intravital microscopy by placement in a tissue bath. Arterioles (9-70 micrometers diam) at several anatomic levels were observed during the initial period of urethan-chloralose anesthesia (period 1), after recovery from the anesthesia (period 2), and again following reanesthetization (period 3). During period 2, respiratory rate, heart rate, and mean arterial pressure were significantly greater than during periods 1 and 3. Smaller arterioles (8-50 micrometers diam) exhibited vasomotion (mean amplitude 35% of mean diameter; mean frequency 31 cycles/min) during period 2. Urethan-chloralose anesthesia during periods 1 and 3 inhibited vasomotion and increased arteriolar diameters by 16-36%. This study quantitates the depressant effects of urethan-chloralose anesthesia on the cardiovascular system and demonstrates the feasibility of using decerebration to circumvent the necessity of continuous drug anesthesia for in vivo microvascular studies.

Local administration of pitrakinra to the lung is sufficient to inhibit AHR, one of the cardinal features of asthma, indicating the therapeutic potential of inhaled pitrakinra in the treatment of atopic asthma.

Hypertension is highly prevalent in elderly individuals and may be associated with cognitive decline, but the mechanisms by which hypertension may impact brain structure, and thereby modulate the time course of late-life cognitive performance, are not well understood. Therefore we used Localized Components Analysis, a novel computational method, to measure spatially-localized patterns of corpus callosum (CC) atrophy in 28 right-handed female subjects aged 75-79 years in the Age, Gene/ Environment Susceptibility-Reykjavik Study (AGES-Reykjavik), a large-scale epidemiological study of aging. Localized callosal atrophy in the posterior midbody and splenium was significantly associated with systolic blood pressure in linear statistical models that controlled for age, while associations between blood pressure and anterior CC atrophy measures were not statistically significant. Additionally, overall measures of global CC atrophy were not significantly associated with blood pressure. The posterior CC may be differentially vulnerable to hypertension-associated atrophy, possibly due to its relatively tenuous vascularization.

Limited information has been published on the use of cardiac troponin I (cTnI) as a biomarker of cardiac injury in monkeys. The purpose of these studies was to characterize the cTnI response seen in cynomolgus macaques during routine dosing and blood collection procedures typically used in preclinical safety studies and to better understand the pathogenesis of this response. We measured cTnI using two different methods, the Siemens Immulite cTnI assay and the more sensitive Siemens Troponin I-Ultra assay. We were able to demonstrate that after oral, subcutaneous, or intravenous dosing of common vehicles, as well as serial chair restraint for venipuncture blood collection, that minimal to mild transient increases in cTnI could be detected in monkeys with both assays. cTnI values typically peaked at 2, 3, 4, or 6 hr after sham dosing and returned to baseline at 22 or 24 hr. In addition, marked increases in heart rate (HR) and blood pressure (BP) occurred in monkeys during the restraint procedures, which likely initiated the cTnI release in these animals. Monkeys that were very well acclimated to the chairing procedures and had vascular access ports for blood sampling did not have marked increases in HRs and BP or increases in cTnI.