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Inhaled endotoxin, lipopolysaccharide (LPS), has been shown to result in bronchial hyperresponsiveness (BHR) to endogenous bronchoconstrictive mediators such as histamine. To determine the role of sensory neuropeptides released from bronchopulmonary C-fibers in LPS-induced BHR, 24 guinea pigs were allocated randomly to the following four groups. Animals in Groups I and IV were challenged with intratracheal instillation of 100 microliters of saline vehicle, and those in Groups II and III with 1 mg of LPS (Escherichia coli, 0111:B4) in 100 microliters of saline. Groups III and IV also received a high dose capsaicin (HDC) treatment to deplete tachykinins from C-fibers 1-2 weeks prior to the experiment. Animals were anesthetized and paralyzed, and total lung resistance (RL) and compliance (Cdyn) were measured continuously during the experiment. Dose responses of RL and Cdyn to histamine (0-8 micrograms/kg, intravenously) and capsaicin (0-1.6 micrograms/kg, intravenously), a specific C-fiber stimulant, were obtained prior to and at 1, 2, and 3 h following LPS/saline vehicle challenge. At 2 h after LPS, delta RL caused by histamine (8 micrograms/kg) was significantly higher in Group II (1.145%) than that in Group I (280%; p0.05); similarly, delta RL caused by capsaicin (1.6 micrograms/kg) was also increased after LPS (Group I, 107%; Group II, 267%; p0.05). Although HDC treatment completely abolished the bronchomotor response to capsaicin in both Groups III and IV, it enhanced the LPS-induced BHR to histamine (8 micrograms/kg; Group III, 1.834%; p0.05). In conclusion, these results suggest that the role of tachykinins in LPS-induced BHR may be dependent upon the type and the route of administration of the bronchoactive substance studied.

Purpose: The aim of this project was to evaluate the feasibility of aortoscopy for guidance of endoluminal aortic procedures and to determine whether aortoscopy has advantages over fluoroscopy in a pig model. Methods: To establish feasibility aortoscopic guidance was used for making endoluminal aortic measurements, cannulating small arteries for arteriograpy, and placing intraaortic stents and grafts in 11 pigs. To compare aortoscopy and fluoroscopy measurements were made and stents were placed by a surgeon using only aortoscopic guidance in 10 pigs and by an interventional radiologist using only fluoroscopic guidance in 10 pigs. Postmortem dissections were performed to determine measurement and device placement accuracy. Results: In the feasibility study aortoscopic measurements differed from postmortem measurements by a mean distance (±SD) of 1.2 ± 0.2 mm. Stents and grafts were placed a mean of 2.3 ± 1.9 mm distal to the most inferior renal artery with no stent covering an orifice. All attempts at cannulating spinal arteries greater than 2 mm in diameter were successful. In the comparison of aortoscopic and fluoroscopic guidance, fluoroscopic measurements differed from postmortem measurements by 2.6 ± 2.4 mm ( p = 0.223). Stents placed with aortoscopic guidance were 1.1 ± 1.3 mm distal to the most inferior renal artery, whereas stents placed with fluoroscopic guidance were 3.4 ± 2.5 mm distal to the most inferior renal artery ( p = 0.019). Conclusions: These results demonstrate that aortoscopy is a useful guidance system for endoluminal aortic procedures and may have advantages over fluoroscopy alone. (J Vasc Surg 1996;24:439-48.)

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.

Somatostatin and its analogue, octreotide acetate, are thought to decrease mesenteric blood flow; however, it is unknown whether the decrease occurs at the central, regional, or microvascular level. We hypothesized that the circulatory effects of octreotide are regulated at the microvascular level. Changes in superior mesentery artery (SMA) flow in response to octreotide were measured with a perivascular ultrasonic flow probe. In separate experiments, the jejunal microcirculatory effects of octreotide were studied using in vivo videomicroscopy. After accrual of baseline hemodynamic and microcirculatory data, animals were randomized to control or treatment (10 micrograms/kg octreotide) iv groups. Measurements were made every 15 min during the infusion and for 90 min after the completion of the infusion. Results are expressed as means +/- SEM. Intravenous infusion of octreotide caused no significant change in arterial pressure, cardiac index, or systemic vascular resistance index in either group in either set of experiments. A statistically significant decrease in heart rate (9%) occurred in the control group of animals undergoing SMA flow measurement. SMA flow did not change significantly with infusion of octreotide. In contrast, jejunal first-order arteriole flow increased to 117.9 +/- 9.7% of baseline (P0.05) in the absence of significant changes in microvessel diameters. This was due to an increase in centerline red cell velocity (116 +/- 5% of baseline, P0.05). We conclude that octreotide increases jejunal first order arteriole flow by mechanisms that are regulated at the microcirculatory level.

Early septic shock is characterized by fever, increased cardiac output, decreased systemic vascular resistance, and dilation of higher-order arterioles in peripheral tissues, such as skeletal muscle. We used a rat model of low-dose lipopolysaccharide (LPS) "septic" shock to investigate the potential benefit of an anti-lipid A monoclonal antibody preparation (E5) on macro- and microcirculatory function. Twenty-five male Sprague-Dawley rats were anesthetized and instrumented for measurement of arterial pressure (AP), heart rate (HR), and cardiac output (CO). The left cremaster muscle of each rat was prepared for in vivo video microscopic examination of changes in third-order arteriolar (A3) diameter and erythrocyte velocity. Rats were randomly assigned to two groups: Group I (n = 13) received E5 vehicle and 200 micrograms/kg Escherichia coli LPS; Group II (n = 12) received 2 mg/kg E5 iv prior to LPS administration. All variables were recorded at 15-min intervals for 30 min prior to and 150 min following LPS. Microcirculatory recordings were restricted to those rats where arteriolar diameters were 20-40 microns and vessels displayed obvious vasomotion (n = 7/group). Infusion of LPS caused no significant change in AP, an increase in CO by 105 min, an increase in HR by 75 min, an increase in diameter by 75 min, and a decrease in velocity by 165 min (P0.01). Pretreatment with E5 inhibited the A3 vasodilation but did not affect the macrocirculatory changes. These data suggest a potential therapeutic role for E5 in ameliorating LPS-induced changes in skeletal muscle microcirculation.

We investigated the use of gamma scintigraphy to evaluate the temporal and spatial patterns of translocation of radiolabeled Escherichia coli from the porcine jejunum during and following hemorrhagic shock. Thirteen healthy mixed breed pigs (22-43 kg) were randomly allocated to two groups. Pigs were anesthetized with sodium pentobarital (30 mg/kg) and mechanically ventilated (100% O2). Each pig was instrumented for mean arterial pressure (MAP) and superior mesenteric artery (SMA) blood flow determination. A 25-cm loop of vascularly intact distal jejunum was isolated, and 10 mCi (10(11) cfu) of radiolabeled E. coli (99mTcO4-) was placed within the bowel segment. Consecutive 5-min scintigrams of the entire abdomen and thorax were collected for 6 hr. Pigs in the shock group (n = 7) were hemorrhaged such that MAP was maintained at 50-60 mm Hg for 5 hr. Pigs in the sham group (n = 6) were maintained without hemorrhage for 6 hr. The total radioactive counts in the translocation regions of the scintigram were plotted against time, and the slope of the regression lines was compared between groups. In the shock group, SMA blood flow decreased significantly (P < 0.05) during the hypotensive period but returned above baseline during reperfusion. The mean (+/- SD) slopes for translocation regression lines were 9.3 +/- 11.4 counts/min and 36.3 +/- 33.7 counts/min in the sham and shock groups, respectively (P < 0.05). Translocation was scintigraphically evident 50-100 min following induction of hemorrhage and did not require reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)