摘要:

The effect of feeding a diet supplemented with lipids and containing 2% cholesterol on the endothelium-dependent relaxation of rabbit aorta to acetylcholine was assessed. The effect of feeding a standard rabbit diet after an initial period of 2% cholesterol feeding was assessed also. Age-matched male, New Zealand white rabbits were fed either a 2% cholesterol diet or a standard rabbit diet. The animals were-anesthetized with pentobarbitone sodium (25 mg/kg) and killed either at the beginning of the study (0 weeks) or at 4, 8, or 10 weeks. The animals in the reversal study were fed the 2% cholesterol diet for 6 weeks and killed after an additional 14 and 32 weeks on standard diet. The extent of atherosclerosis in the aorta was assessed by Sudan Red staining, estimation of tissue cholesterol, and light and electron microscopy. The relaxation response to acetylcholine was measured in rings of the thoracic aorta following precontraction with norepinephrine (−6.0 log mol/1). The relaxation was significantly impaired in aortas from rabbits fed the 2% cholesteroldiet compared to aortas from animals fed the standard diet. The impairment of relaxation was apparent as early as 4 weeks after the start of the 2% cholesterol diet and remained impaired over the next 6 weeks. No improvement in endothelium-dependent relaxation was seen in rabbits on the reversal diet for 14 and 32 weeks. Thus, endothelium-dependent relaxation is attenuated in animals fed a 2% cholesterol diet, and the loss of relaxation persists for at least 32 weeks after the animals are returned to a standard diet.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The return of fluid and protein to the bloodstream by the lymphatic circulation may play an important role in reconstituting intravascular volume following hemorrhage. In this study, we have defined the lymph-flow changes that occur in cannulated mesenteric lymphatics following a 25% blood loss in anesthetized sheep and investigated the effects of hemorrhage on the intrinsic contractile activity (lymph pumping) of these vessels in vivo using a new model system. The removal of 25% of the calculated blood volume resulted in increases in lymph flow over a 6-hour period, with peak changes to 3.5 times the prebleed levels. Systemic arterial pressures dropped to roughly 50% of control values immediately following the bleed and returned to control in 3 hours. To directly assess the effects of hemorrhage on lymphatic pumping, a segment of intestinal lymphatic was isolated from all lymph input and supplied with fluid from a reservoir. While there was no net pressure driving fluid through the duct, a transmural distending pressure was applied to the vessel, which stimulated resting lymphatic contractions and fluid pumping. A 25% blood loss resulted in increased activity of the lymph pump; up to 6 times more fluid was propelled through this “isolated” vessel in vivo than in similar preparations in sheep that were not bled (p<0.01). Measurements of fluid pulse pressures in this preparation indicated increased pumping frequency and/or force after hemorrhage compared with prebleed levels. We conclude that lymphatic contractile activity is stimulated after a blood loss independent of changes in lymph formation and speculate that this mechanism may play an important role in the reexpansion of the vascular space.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Although previous studies have proposed a variety of models to characterize diastolic pressure-flow relations, the models' ability to predict capacitance-free pressure-flow relations from dynamic information in individual studies has not been determined. This study tested the ability of a lumped RC model with pressure-dependent parameters to predict diastolic capacitance-free flow during maximum vasodilation in anesthetized dogs. Model parameters were characterized by perturbing the circumflex coronary artery with a ramp pressure waveform that caused coronary artery pressure to decline at rates varying from 30–150 mm Hg/sec. Capacitance-free relations constructed from declining and rising ramp pressure-flow data corresponded with capacitance-free pressure-flow points constructed during constant-pressure coronary artery perfusion (which are model-independent). The model parameters derived from analysis of the ramp data indicate that conductance of the coronary bed varies directly with coronary pressure and is independent of the rate of coronary pressure decay. Values of coronary capacitance vary inversely with coronary artery pressure and with the magnitude of dPix/dt. Thus, a simple, lumped diastolic model with pressure-dependent parameters can predict capacitance-free pressure-flow behavior from dynamic pressure-flow data and characterize model parameters over a wide range of coronary pressure.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The abnormalities in regional function produced by myocardial ischemia persist after the ischemic episode resolves. Since a close functional coupling exists between myofibrillar creatine kinase and myosin ATPase, a disruption of this coupling could adversely influence myocardial function and might provide a mechanism for the myocardial dysfunction observed. The purpose of the present study was to determine if an alteration in the activity of creatine kinase associated with the myofibril occurs in the postischemic period. Anesthetized open-chest dogs (n = 6) underwent coronary occlusion for 15 minutes, followed by reperfusion for 15 minutes. In reperfused myocardium, adenine nucleotide content was decreased (72 ±10% of noniscbemk myocardium, p<0.05), documenting the presence of previous ischemia. The creatine phosphate content of reperfused myocardium returned to normal, indicating resumption of myocardial energy production. The creatine kinase activity of purified myofibrils isolated from reperfused myocardium was decreased by 17 ± 7% compared to that of nonischemic myofibrils (p<0.03). In addition, the free adenosine diphosphate concentration in reperfused myocardium was calculated to be 96 μIM and was less than the Km of adenosine diphosphate determined for myofibrillar creatine kinase (105 μM). The results suggest two putative mechanisms for disruption of energy use in postischemic myocardium: decreased creatine kinase activity associated with the myofibril, and limitation of substrate necessary for maximal creatine kinase activity.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Recently, total chemical synthesis of thromboxane was achieved. The in vitro activity of synthetic thromboxane A2is indistinguishable from biologically generated material. The present study describes the in vivo characterization of synthetic thromboxane A2on the regional blood flow distribution of the canine heart. Local injections of synthetic thromboxane A2into the coronary vasculature caused marked reductions in coronary blood flow, measured by both radiolabeled microsphere injection and an electromagnetic flow device. The threshold concentration required to bring about this effect varied greatly between dogs and ranged from 0.125 μg/kgto 2.0 μg/kg. Similarly, the dose of thromboxane A2required to aggregate dog platelets in vitro varied from 30 ng/ml to 1,000 ng/ml. Bolus injections of 2 μg/ml thromboxane A2into the circumflex or left anterior coronary artery resulted in a simultaneous reduction in platelet count in coronary sinus blood of 83 ± 5.2% (mean ± SEM,n= 4,p= .0005). Both flow reduction and platelet effects were transient and localized. The time taken from onset to recovery of the response to control levels was 77 ± 6.0 seconds (mean ± SEM) for flow and 70–80 seconds for platelet count. Injections of thromboxane A2caused a small but significant increase in heart rate with no change in systemic blood pressure. In conclusion, the in vivo actions of synthetic thromboxane A2are consistent with the vasoconstrictor and platelet aggregatory effects seen in vitro, but dogs vary considerably in their sensitivity.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Previous studies on the pressor response of the newborn pulmonary circulation to hypoxia have used intact animals and have reported conflicting results. Some have found an increase in responsiveness with increasing age; others have found a decrease. To circumvent many problems inherent in studies of pulmonary vascular reactivity in intact animals, we have developed methods for studying isolated, blood-perfused lungs from newborn rabbits. These methods have been used to study the influence of postnatal age on hypoxic pulmonary vasoconstriction. Two sets of experiments were performed. In the first, a stimulus response curve for hypoxic pulmonary vasoconstriction was constructed, using lungs from 19 rabbit pups that were 3–8 days old. At a constant blood flow, pulmonary artery pressure increased progressively as alveolar oxygen tension decreased so that the maximum increase from baseline (29.4 ± 4.7%) occurred at P1o2= 0. The pressor response to hypoxia was highly reproducible, and the entire system remained stable for over 2–3 hours. In the second set of experiments, we compared the pulmonary vascular response to hypoxia obtained using lungs from an additional 21 pups that were 3–8 days old with that obtained using lungs from 23 pups that were 10–14 days old. In response to the same hypoxic stimulus, pulmonary artery pressure increased more in lungs from older rabbit pups (56 ± 4%) than in lungs from younger rabbit pups (34 ± 7%) (p <0.001). We conclude that isolated perfused lungs from newborn rabbits exhibit a reproducible pressor response to alveolar hypoxia and that this response increases as a function of postnatal age.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The small molecular weight peptide, atrial natriuretic peptide (ANP), produces marked sodium and water excretion. The peptide, extracted from several species of vertebrate heart, also has been shown to increase glomerular filtration and reduce plasma volume. Several mechanisms have been proposed to account for the action of the peptide but remain undefined. In the present report, the ANP-induced alterations in transcapillary water movement were directly assessed. The modified Landis technique was used to measure single capillary hydraulic conductivity (Lp) of vessels from the frog mesenteric circulation. In 6 individual microvessels, Lp was measured under control conditions and again during perfusion with 10 × 10-6 M ANP. The Lp increased in each vessel by a mean of 3.79-fold (± 2.09 SD). In 4 of these vessels, an additional measurement of Lp was repeated under control conditions; the capillary filtration coefficient returned to control levels. It was concluded that ANP directly and reversibly elevates capillary hydraulic conductivity; this response is independent of changes in capillary hydrostatic pressure or surface area.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID