摘要:

This study was aimed at defining the role of vascular endothelium in the transport and metabolism of adenosine. For this purpose, endothelium-intact and endothelium-denuded isolated rat aortas, perfused at constant flow (2 ml/min), were prelabled with3H-adenosine or3H-inosine for 10 minutes at concentrations of 0.012-100 μM. Sequestration of adenosine by endothelium was determined from radioactivity recovered during selective endothelial cell removal with deoxycholic add (0.75percent; for 15 seconds). In the physiological concentration range of adenosine (0.012- -1 üM), fractional sequestration by endothelium was 90–92percent; of the total adenosine incorporation by the aorta. Endothelial sequestration of inosine at 0.1 üM was 85percent;. At 100 üM adenosine or inosine, fractional sequestration by aortic endothelium was 33percent; and 39percent;, respectively. Analysis of the specific radioactivity of adenine nucleotides extracted from prelabeled aortas indicated that most of the adenosine was incorporated into endothelial adenine nudeotides. Incorporation of inosine into endothelial ATP was approximately 15percent; that of adenosine. Ininbition of aortic adenosine deaminase with erythro-9-(2-hydroxy-3-nonyI)adenine (EHNA) did not influence sequestration of 0.1 üM adenosine, but resulted in a 49percent; reduction of total endothelial incorporation at 100 üM adenosine. Transfer of radioactive purines from the endothelium to underlying smooth muscle after prelabeling was equivalent to only 1percent;/hr of total endothelial radioactivity. Our findings suggested that 1) macrovascular endothelium of the aorta constitutes a highly effective metabolic barrier for circulating adenosine and inosine; 2) transfer of labeled adenine nucleotides from endothelium to underlying smooth muscle is rather small and most likely proceeds via dephospborylated purine compounds; and 3) measurement of adenosine trapping in endothelial and smooth muscle compartments overestimates the transendothelial adenosine concentration gradient.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

This study was designed to define the effect of postischemic low Ca2+perfusion on recovery of high-energy phosphates, intracellular pH, and contractile function in isolated rat hearts. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to follow creatine phosphate, adenosine triphosphate, intracellular inorganic phosphate, and intracellular pH during control perfusion (15 minutes), total ischemia (30 minutes), and reperfusion (30 minutes). In Group I the perfusate [Ca2+] was 1.3 mmol/1 throughout the experiment, whereas in Group II the perfusate [Ca2+] was reduced to 0.05 mmol/1 during the first 10 minutes of reperfusion. Hearts from Group III were not made ischemic but were subjected to 10 minutes of low Ca2+perfusion followed by 20 minutes of normal Ca2+perfusion. During low Ca2+reperfusion (Group II) recovery of high-energy phosphates and pH was significantly better than in controls (Group I). However, after reexposure to normal Ca2+, metabolic recovery was largely abolished, coronary flow was suddenly impaired, and contracture developed without any rhythmic contractions. These observations indicated the occurrence of a calcium paradox rather than postponed ischemia reperfusion damage. On the other hand, normoxic hearts (Group III) tolerated temporary perfusion with 0.05 mmol/1 Ca2+very well with respect to left ventricular developed pressure, coronary flow, and metabolic parameters. In conclusion, postischemic low Ca2+(0.05 mmol/1) perfusion may reduce reperfusion damage, but at the same time ischemia appears to enhance the susceptibility of the heart to the calcium paradox.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Lymphatic pumping activity was examined in halothane-anesthetized sheep. A doubly cannulated preparation of the mesenteric lymph duct was "isolated" from lymph input, other than that from a constant pressure reservoir of artificial lymph attached to its inflow cannula, but had its blood supply and innervation intact. A cerebral ischemic response, evoked by injection of 2 ml air into the common carotid artery, increased both mean arterial pressure and fluid propulsion by the lymphatic. The latter rose from a control value of 45 μl/min to a peak of 74 μl/min. When 10-4M phentolamine was Introduced into the lymphatic lumen, there was a transient increase followed by a sustained fall in lymph pumping. Repetition of the air injection while phentolamine was present in the duct lumen produced no increase in lymph pumping. In adrenalectomized animals, resting lymph propulsion by the mesenteric duct was depressed, and the response to air injection was attenuated but remained significantly greater than control. These results suggest that reflex activation of the sympathetic nervous system can increase lymph propulsion and that this may be augmented by the release of circulating catecholamines.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Newly developed biphasic waveforms improve defibrillation efficacy both by reduction of defibrillation threshold and by amelioration of shock-induced dysfunction depending on the relative shape of the first and second pulses. Each of these independent effects improves the waveform's safety factor, the ratio between the shock intensity that produces a specific degree of postshock dysfunction and the shock intensity that produces defibrillation (or cellular excitation). Symmetrical waveforms reduce defibrillation threshold to about 60percent; that of the corresponding monophasic waveform, probably by reduction of excitation threshold for ischemic cells, but increase postshock arrhythmias. Biphasic waveforms with 10percent; "tails" reduce postshock arrhythmias. This study tests the hypothesis that these independent mechanisms for improvement of defibrillation efficacy can be combined into a single triphasic waveform that will have a highers afety factor than either of the two biphasic waveforms of which it is composed. Cultured myocardial cells were subjected to high-intensity electric-field stimulation with a control monophasic rectangular waveform, a symmetrical biphasic waveform, and a triphasic waveform consisting of the biphasic waveform with an added 10percent; "tail." Each waveform portion was 5 msec in duration. Photocell mechanograms monitored contractile activity. We found that the duration of postshock arrest of spontaneous contractile activity increased with stimulus intensity for all waveforms. The voltage gradient producing a 4-second arrest after the biphasic waveform shock was 80.6±1.3percent; that of the control waveform (100percent;), while the voltage gradient for the triphasic waveform was 87.1 ±0.73percent; of control. The difference between biphasic and triphasic waveforms was significant (p<0.001). Relative excitation thresholds for the biphasic and triphasic waveforms were each 67percent; that of the monophasic waveform and did not differ significantly. Relative safety factor for the biphasic waveform was 120.3 and that for the triphasic waveform was 130.0 compared with a value of 100 for the control monophasic waveform. These results suggest that triphasic waveforms decrease postshock arrhythmias and increase the safety factor for defibrillation.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Lower torso ischemia and reperfusion lead to respiratory dysfunction characterized by pulmonary hypertension and increased lung microvascular permeability. This is associated with lung leukose- questration and thromboxane (TX) generation. This study tests the role of elevated TX levels following muscle ischemia in mediating remote lung injury. Anesthetized sheep prepared with chronic lung lymph fistulae underwent 2 hours of bilateral hind limb tourniquet ischemia. In untreated controls (n=7), 1 minute after reperfusion there was a transient increase in plasma immunoreactive (i)-TXB2levels from 211 to 735 pg/ml (p<0.05), and at 30 minutes, lung lymph i-TXB2levels rose from 400 to 1,005 pg/ml (p<0.05). At 1 minute, the mean pulmonary arterial pressure (MPAP) increased from 13 to 38 mm Hg (p<0.05) and pulmonary microvascular pressure (Pmv) from 7 to 18 mm Hg (p<0.05). Lung lymph flow (QL) rose from 4.3 to 8.3 ml/30 min (p<0.05), the lymph/plasma (L/P) protein ratio was unchanged from 0.6, and the lymph protein clearance increased from 2.6 to 4.6 ml/30 min (p<0.05). Two hours after reperfusion, neutrophils were observed sequestered in lung capillaries and protemaceous exudates were found in alveoli in contrast to sham-operated animals (n=3). To maximize lung vascular surface area and acineve a pressure independent L/P protein ratio a left atrial balloon was inflated during one group of ischemia-reperfusion experiments (n=5). This resulted in a baseline rise in MPAP to 20 mm Hg (p<0.05); a 4.3-fold increase in QL (p<0.05), a decrease in the L/P ratio from 0.70 to 0.28 (p<0.05) and a protein reflection coefficient (ód) of 0.72. During reperfusion the L/P ratio rose to 0.49 (p<0.05) and the ód decreased to 0.51 (p<0.05), documenting an increase in lung microvascular permeability. In contrast to untreated ischemk controls, ininbition of TX synthetase with OKY 046 (n=6) reduced plasma i-TXB2levels to 85 pg/ml (p<0.05) but also increased i-6-keto-PGF1αlevels to 78 pg/ml relative to 15 pg/ml in untreated controls (p<0.05). OKY 046 prevented the increase in MPAP, Pmv, QL, and lymph protein clearance (p<0.05). Lung histology was normal in distinction to the leukosequestration in untreated ischemic controls. Pretreatment with OKY 046 combined with ibuprofen (n=5) prevented the increase in i-6-keto-PGF1α(p<0.05) but still led to a response unchanged from OKY 046 treatment alone. Pretreatment with the TX receptor antagonist SQ 29,548 (n=5) did not affect the ischemia induced increases in TXB, levels in plasma and lung lymph to 702 and 789 pg/ml, respectively, but prevented the increase in MPAP, Pmv, QL, lymph protein clearance, and lung leukosequestration (p<0.05 for all). These data indicate that the increased lung permeability following lower torso ischemia and reperfusion may be mediated by TX.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

A new protocol has been developed for selective removal of the endothelium from the arteries of the perfused rat hind-limb preparation. The hind limb was perfused with oxygenated Krebs-Ringer bicarbonate solution with a combination of high flow and timed air bubbles (2 minutes at high flow followed by 5 minutes of air bubbles, followed by a further 2 minutes at high flow). Representative vessels at different diameters of the arterial tree–-the femoral artery, the artery supplying the extensor hallucis proprius muscle, and the arteries, arterioles, and capillaries withinthe hallucis proprius muscle–-were taken for examination by transmission and scanning electron microscopy. A graded degree of damage occurred along the length of the hind-limb vasculature, with endothelial cells having been completely removed from the femoral artery, removed from or severely damaged in the artery supplying the hallucis proprius muscle, and partially damaged in arteries within the hallucis proprius muscle. However, no damage occurred to the endothelial cells of the arterioles and capillaries within the hallucis proprius muscle. The integrity of the vascular bed after endothelial removal according to the above protocol was confirmed by the demonstration of no diminution, but in fact an increase, in contractile responses to bolus injections of α,β-methylene ATP, resulting in a shift to the left of the dose-response curve. The viability was further confirmed by the fact that the conductance (flow/perfusion pressure) of the preparation during the periods of high flow was no different before and after removal of the endothelium. In conclusion, the high flow/air bubbles/high flow protocol can be used to selectively remove endothelial cells from the arteries of the rat innd-limb preparation without damage to the endothelium of arterioles and capillaries or to smooth muscle cells.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effect of stimulation of the cervical sympathetic ganglia on the upper limit of cerebral blood flow (CBF) autoregulation was studied in normotensive Wistar-Kyoto rats (WKY) and in spontaneously hypertensive rats (SHR) following intravenous administration of the angiotensin converting enzyme ininbitor captopril (10 mg/kg). CBF was measured using the intracarotidl33Xe injection method in halothane/nitrous oxide anaesthetized WKY and SHR. Arterial blood pressure was raised stepwise by the intravenous infusion of noradrenaline. Toward the end of the study, Evans blue was injected and the brains examined for gross blood-brain barrier breakdown. In SHR, sympathetic stimulation reextended the upper limit of CBF autoregulation, which was at a mean arterial blood pressure level of 120–139 mm Hg in the control group of eight SHR and above 170 mm Hg in the stimulated group of nine SHR. In the group of nine WKY subjected to sympathetic stimulation, the upper limit of CBF autoregulation was reached at a mean arterial blood pressure level of 110–129 mm Hg as opposed to 90–109 mm Hg in a previous unstimulated group of WKY. In the two groups subjected to sympathetic stimulation, there was no extravasation of Evans blue in any of the brains. In the control group of SHR, in which there had been marked increases in CBF, three out of eight brains had foci with extravasation of the dye. It is concluded that in normotensive and in hypertensive rats sympathetic stimulation attenuates the downward shift of the upper limit of CBF autoregulation, which is known to accompany intravenous administration of captopril.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We have previously reported that chronic bradycardial pacing increases both capillary density/ mm2(CD) and maximal work output in normal rabbit hearts. This technique has now been applied to rabbits with volume-overload hypertrophy due to lesion of the aortic valve. Four groups of animals were studied: controls (C), paced (P), valve-lesioned (VL), and paced valve-lesioned (PVL). The aortic valve was lesioned 8 weeks before the acute experiments; pacing was started 4 weeks before the acute experiments, and thus, the PVL group had developed hypertrophy before pacing was started. The degree of hypertrophy was similar in VL hearts whether paced or not: heart wt/body wt ratio increased by 33.5±8.9percent; (mean±SEM) in VL and 25.2±8.2percent; in PVL versus control animals of similar body weight (p<0.001). The hearts of the PVL animals showed a higher CD (2,277±107) than VL hearts (1,383±43), CD in C hearts of similar weights being 1,595±103, and in P hearts 2,350±194. Thus, CD was lower by 14percent; in VL and higher by 43percent; in PVL than in C hearts. Valve-lesioning had a significant effect in reducing maximal cardiac minute work (p<0.001), whereas pacing significantly unproved maximal cardiac minute work (p<0.001) to 2.467±0.206 J/gX10-4in the P group versus 1.609±0.105 in the C group. In the valve-lesioned hearts, work levels were normal after pacing (1.613±0.152 J/ gX10-4) compared with the lower maximal cardiac minute work in hypertrophy alone (1.102±0.162). Chronic bradycardial pacing, therefore, reversed what was a small deficit in capillary density to a substantial increase and significantly unproved maximal cardiac minute work performance in hypertrophied hearts.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The present study documents the permeability characteristics of heart valvular endothelium to low-density lipoprotein (LDL), albumin, and horseradish peroxidase (HRP). Using quantitative autoradiography, LDL and albumin concentrations were measured within aortic valves of squirrel monkeys and rabbits after 30 minutes of in vivo circulation. The valvular concentration profiles were analyzed using theoretical mathematical models based on fundamental transport principles. In vivo transvalvular concentration profiles of LDL and albumin displayed the highest tissue concentrations immediately beneath the endothelium and displayed the lowest concentrations near the midline of the valve. Tissue concentrations of LDL and albumin displayed large differences in magnitudes between different regions of individual valve leaflets suggesting marked spatial variation in the permeability properties of the valvular endothelium to LDL and albumin; this was also seen visually with HRP. The results of the theoretical analysis showed that 1) the aortic valvular endothelium limits the uptake of LDL and albumin into the valvular tissue, 2) the permeability of the valvular endothelium differs widely from one region of a valve to another and even from one side of the valve to the other within a single valvular region, and 3) intramural diffusion is the predominant mode of transport for LDL and albumin within the aortic valve, even in valvular regions exposed to large pressure differences across the valve.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Angiotensin II may contribute to the progression of renal glomerular diseases. Beneficial effects of converting enzyme inhibition in models of renal disease are, however, not always explicable by hemodynamic consequences of angiotensin II inhibition. Angiotensin increases intracellular calcium in glomendar mesangial cells and activates phospholipase A2, factors required for the formation of the lipid mediator of Inflammation platelet activating factor (PAT). We therefore examined whether angiotensin II could stimulate PAF production in cultured rat mesangial cells. During a 15-minute incubation angiotensin II caused formation of PAF in a dose- dependent manner with a threshold around 10-9M. In four experiments PAF formation in response to angiotensin II (10-8M) occurred within 5 minutes and was 29±8 pmol PAF/mg protein. The amount of PAF detected then declined to 9±2 and 13±3 pmol after 15 and 30 minutes of incubation with angiotensin II. More than 90percent; of the PAF remained cell-associated. The PAF formation was confirmed by negative ion chemical ionization mode of mass spectrometry. A single species of PAF was detected and identified as hexadecyl PAF. We speculate that part of the detrimental effects of angiotensin II in progressive renal disease may relate to PAF formation. The PAF generated may in turn influence glomendar function, platelets, and eicosanoid synthesis, all factors implicated in renal disease. Furthermore, we speculate that angiotensin II-induced PAF formation may contribute to microvasculature pathology in general.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID