The American journal of physiology
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Mechanisms of circulatory effects induced by nitric oxide synthase inhibition in endotoxemia were investigated in 36 pigs randomized to 1) endotoxin infusion (1.7 micrograms.kg-1.h-1 iv) for 7 h and bolus NG-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg iv) after 3 h; 2) endotoxin infusion for 7 h; 3) saline infusion for 7 h and L-NAME after 3 h; and 4) saline infusion for 7 h. Fifteen minutes after L-NAME injection during endotoxemia, reductions in cardiac output (41%, P < 0.05), portal venous flow (51%, P < 0.05), and hepatic artery flow (50%, P < 0.05) were observed. Systemic vascular resistance increased by 82% (P < 0.05), and the portocaval vascular resistance increased by 101% (P < 0.05). ⋯ In conclusion, L-NAME decreased intravascular blood volume and increased splanchnic venous resistance. These effects will tend to reduce venous return. Combined with a marked increase in left ventricular after-load, L-NAME may thus compromise cardiovascular function in endotoxemia.
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It has been suggested that pulmonary artery pressure at the end of ejection is close to mean pulmonary artery pressure, thus contributing to the optimization of external power from the right ventricle. We tested the hypothesis that dicrotic notch and mean pulmonary artery pressures could be of similar magnitude in 15 men (50 +/- 12 yr) referred to our laboratory for diagnostic right and left heart catheterization. Beat-to-beat relationships between dicrotic notch and mean pulmonary artery pressures were studied 1) at rest over 10 consecutive beats and 2) in 5 patients during the Valsalva maneuver (178 beats studied). ⋯ The slope of this relation had the dimension of a volume elastance (in mmHg/ml), a simple estimate of volume elastance being obtained as 1.06(PVR/T), where T is duration of the cardiac cycle. In conclusion, dicrotic notch pressure was of similar magnitude as mean pulmonary artery pressure. These results confirmed our primary hypothesis and indicated that human pulmonary artery can be treated as if it is an elastic chamber with a volume elastance of 1.06(PVR/T).
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Sepsis is believed to induce disturbances in microcirculatory flow and nutrient exchange, which may result in impaired tissue oxygenation. With the use of an established rat model of endotoxemia, voltametric measurements were made of skeletal muscle (tissue) oxygen tension (PtO2) and its response to inspired oxygen concentration (FIO2). Steady-state nutritive flow and the response of endotoxemic muscle to ischemia-reperfusion were also measured. ⋯ Endotoxemic muscle PtO2 values showed less heterogeneity than control groups and significant attenuation of the response to increasing FIO2 to 0.95 (mean rise in PtO2 +/- SE; 27 +/- 7 vs. 80 +/- 11 Torr for endotoxemic and control groups, respectively; P < 0.01). No steady-state differences in tissue perfusion or response to ligation-induced ischemia-reperfusion could be demonstrated between endotoxemic and control rats. These data suggest that there is significant tissue hypoxia and abnormal microvascular control of oxygenation in endotoxemia, even in the presence of normal microcirculatory perfusion.
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At birth, the rat renal papilla has the structural composition of the mature inner stripe of the outer medulla. All loops of Henle have the configuration of short loops, and there are no ascending thin limbs. This study examines the role of apoptosis in the differentiation of the loop of Henle and the development of the ascending thin limb in the rat kidney. ⋯ This was associated with transformation from a cuboidal to a squamous epithelium and subsequent disappearance of 5-HT1A immunostaining from the transformed cells. Electron microscopy confirmed the presence of apoptotic cells and phagocytosed apoptotic bodies in the thick ascending limb in the renal papilla. We conclude that the ascending thin limb is derived from the 5-HT1A-positive thick ascending limb by apoptotic deletion of thick ascending limb cells and transformation of the remaining tubule cells into the 5-HT1A-negative ascending thin limb.