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This study had two purposes. One was to investigate the placental gradients and the relationship of human chorionic gonadotropin (hCG) concentrations in maternal serum (MS), amniotic fluid (AF) and fetal serum (FS). The other was to study the fetal sex effect. This study included 93 patients with normal singleton term pregnancies. AF samples contaminated with blood were excluded. Fetuses did not have any abnormalities. We measured hCG by double antibody beta hCG radioimmunoassay. We found that there were conspicuous hCG slopes in MS, AF and FS levels. The hCG level in MS was 12.9 +/- 1.3 IU/mL (mean +/- SE, n = 93). It was much higher than levels in AF or FS. AF (0.461 +/- 0.053 IU/mL, n = 25) also had higher hCG level than FS (0.038 +/- 0.0056 IU/mL, n = 93). The hCG concentrations in AF and FS were highly correlated with those in corresponding MS (P < .001 and P < .05, respectively). The concentrations in AF were also positively correlated with those in corresponding FS (P < .05). The mean of MS/AF ratios for hCG was 413.6 +/- 23.4 (+/- SE); of MS/FS, it was 37.8 +/- 9.2; of AF/FS, it was 15.3 +/- 2.6. At late pregnancy, higher hCG levels of MS, AF or FS may result in female fetuses than in male fetuses. The results revealed that there were hCG concentration gradients on both placental and fetal membranes. It also implied that hCG levels in AF may decline as gestation ages advance. For biochemical studies in FS, using pure cord venous blood may have more consistent results than using mixed blood.(ABSTRACT TRUNCATED AT 250 WORDS)
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OBJECTIVE: Conventional extracorporeal circulation results in an activation of coagulation cascades. Coating of extracorporeal circulation tubes as well as avoidance of shed blood recirculation have been shown to reduce these phenomena. We evaluated a new shed blood separation system (AVANT D 970) utilizing a coated cardiopulmonary bypass tube system (PHISIO). METHODS: Forty patients (62 +/- 10 years) underwent isolated coronary revascularization. Four groups (n = 10/group) were defined: no extracorporeal circulation, conventional uncoated extracorporeal circulation, uncoated extracorporeal circulation with shed blood separation, and coated extracorporeal circulation with shed blood separation. Thrombin-antithrombin complex and free Hb were analyzed and statistically compared. RESULTS: Conventional extracorporeal circulation exhibited the highest intraoperative activation of coagulation (thrombin-antithrombin complex: extracorporeal circulation, 31.1 +/- 15.8 microg/L; uncoated extracorporeal circulation with shed blood separation, 15.3 +/- 7.8 microg/L; coated extracorporeal circulation with shed blood separation, 8.1 +/- 4.8 microg/L; no extracorporeal circulation, 2.4 +/- 0.6 microg/L; P <.05 extracorporeal circulation vs all others) and red blood cell damage (free Hb: extracorporeal circulation, 16.8 +/- 11.4 micromol/L; uncoated extracorporeal circulation with shed blood separation, 10.3 +/- 3.5 micromol/L; coated extracorporeal circulation with shed blood separation, 6.8 +/- 2.9 micromol/L; no extracorporeal circulation, 3.4 +/- 1.1 micromol/L; P <.05 extracorporeal circulation vs no extracorporeal circulation, coated extracorporeal circulation with shed blood separation). Coated extracorporeal circulation with shed blood separation showed only slight activation and cell trauma, which did not differ significantly from no extracorporeal circulation. CONCLUSIONS: Combination of coating and avoidance of shed blood recirculation maintained physiological coagulation levels and markedly reduced red blood cell trauma in extracorporeal circulation procedures. These combined modalities may therefore offer an alternative for off-pump procedures in patients with contraindications for conventional extracorporeal circulation.
Circulating concentrations of leptin are better correlated with absolute amounts of adipose tissue [fat mass (FM)] than with relative body fatness (body mass index or percent body fat). There is a clear sexual dimorphism in circulating concentrations of leptin (females > males) at birth and in adulthood. However, whether such dimorphism is present in the interval between these periods of development remains controversial. We examined body composition and clinical (Tanner stage) and endocrine (pituitary-gonadal axis hormones) aspects of sexual maturation in relationship to circulating concentrations of leptin in 102 children (53 males and 49 females, 6-19 yr of age) to evaluate the relationship between circulating leptin concentrations and body composition before and during puberty. Pubertal stage was assigned by physical examination (Tanner staging) and also assessed by measurement of plasma estradiol, testosterone, and pituitary gonadotropins. Body composition was determined by dual-energy x-ray absorptiometry and by anthropometry. Circulating concentrations of leptin in the postabsorptive state were determined by a solid-phase sandwich enzyme immunoassay. The effect of gender on the relationship between circulating leptin concentrations and FM was determined by ANOVA at each Tanner stage. Stepwise multiple linear regression analyses, including circulating concentrations of pituitary-gonadal axis hormones, and FM were performed, by gender, to determine whether the relationship between circulating concentrations of leptin and FM changes during puberty. Plasma leptin concentrations were significantly correlated with FM at all Tanner stages in males and females. Plasma leptin concentrations, normalized to FM, were significantly higher in females than males at Tanner stages IV and V but not at earlier stages of pubertal development. Plasma leptin concentrations, normalized to FM, were significantly greater in females at Tanner stage V compared with females at Tanner stage I and significantly lower in males at Tanner stage IV and V compared with males at Tanner stage I. These significant gender and maturational differences were confirmed by demonstrating that the regression equation relating circulating leptin concentrations to FM in females and males at Tanner stages IV and V were significantly different (predicted lower leptin concentrations in males than females with identical body composition) and that the regression equations relating circulating concentrations of leptin to FM in each gender before puberty (Tanner stage I) were significantly different (predicted higher plasma concentrations of leptin in prepubertal males and lower leptin concentrations in prepubertal females) than the same regression equations in later puberty. Circulating concentrations of testosterone were significant negative correlates of circulating concentrations of leptin normalized to FM in males when considered as a group over all pubertal stages. The inclusion in multivariate regression analyses of circulating concentrations of testosterone and estradiol, FM, fat-free mass, and gender did not eliminate a significant gender-effect (P < 0.05) on circulating concentrations of leptin at Tanner stages IV and V. The circulating concentration of leptin, normalized to FM, declines significantly in males and rises significantly in females late in puberty to produce a late-pubertal/adult sexual dimorphism. These studies confirm a potent role for gonadal steroids as mediators of this sexual dimorphism in circulating concentrations of leptin. (ABSTRACT TRUNCATED)
The IGF-binding proteins (IGFBPs) are a family of at least six structurally related proteins, which bind the IGFs and modulate their actions, including the regulation of pre- and postnatal growth. In this study we have examined the relationship between circulating and tissue mRNA levels of IGFBPs and related this to circulating IGFs in the fetal sheep over the gestational period when rapid growth and development occurs. Circulating IGFBP-2, as measured by Western ligand blot (WLB), increases between early and mid gestation, remains high, then declines throughout late gestation (P = 0.0002). Circulating IGFBP-3 increases throughout gestation, as measured by WLB or RIA (P = 0.04 and P = 0.0001 respectively), as does circulating IGFBP-4 (P = 0.004). These ontogenic changes in circulating IGFBPs-2 and -4 are paralleled by changes in liver mRNA for these proteins and, for IGFBP-2, by those in kidney IGFBP-2 mRNA also. This suggests that liver and kidney may be the primary contributors to circulating IGFBP-2 and the liver to circulating IGFBP-4, IGFBP-2 mRNA is present in the heart and lung in early gestation but barely detectable in these tissues after approximately 60 days gestation. IGFBP-4 mRNA is also present in the heart in early but not late gestation, but is abundant in the lung throughout gestation. These results demonstrate tissue specific and developmental regulation of IGFBPs-2 and -4 at the mRNA level. To assess any role the circulating IGFs may play in mediating these changes in IGFBPs, or vice versa, both plasma IGF-I and IGF-II were measured by RIA. Circulating IGF-I increases as gestation progresses (P = 0.0001), while circulating IGF-II increases between early and mid gestation, remains high (P = 0.01), then declines. Circulating IGF-I is positively correlated with fetal weight (r = 0.66, P = 0.03), circulating IGFBP-3 (r = 0.54, P = 0.01) and IGFBP-4 (r = 0.52, P = 0.01). Circulating IGF-II positively correlates with circulating IGFBP-2 (r = 0.48, P = 0.02) throughout gestation and at 1 day postnatally. These relationships are consistent with circulating IGF-I influencing IGFBPs-3 and -4, and similarly, IGF-II determining IGFBP-2, or vice versa. Alternatively, these correlations may reflect coordinate regulation of IGF and IGFBP by a common factor.
Collateral circulation of angiogram in occlusion of main trunk of the middle cerebral artery in acute stage was studied in detail, and compared with the extent of the low density area on CT. Territory of the middle cerebral artery in the lateral view of angiogram was divided into three regions. Collateral circulation time was measured with the period from the maximum filling of carotid siphon to the retrograde maximum filling of collateral circulation. With these studies, the following conclusions were obtained. 1) The degree of collateral circulation is classified into three types. One type with good collateral circulation is type I. Another type with moderate collateral circulation is type II. A further type with poor collateral circulation is type III. Angiographic circulation time in each branch of the middle cerebral artery is measured in each type. 2) There is a tendency that types with the better development of collateral circulation have the smaller low density area on CT. In type I, the smallest low density area on CT appears in the territory of basal ganglia or around corona radiata. In type II or III, the medium or large low density area on CT appears in cortical and/or subcortical territory of the middle cerebral artery. 3) There is a tendency that types with the worse development of collateral circulation have the later collateral circulation time in each region. If collateral circulation time is later than 4 seconds, it is impossible to avoid the appearance of the low density area on CT in C region. In the same way, in B region, it is later than 5 or 6 seconds, in A region, it is later than 7 seconds. But, in type II or III, there are a few cases in which it is impossible to avoid the appearance of the low density area on CT, even if collateral circulation time is earlier than those mentioned. As mentioned above, classifying of collateral circulation is possible to expect the extent of the low density area on CT, and measurement of collateral circulation time is able to estimate the appearance of the low density area on CT. In type I and II, superficial temporal artery to middle cerebral artery anastomosis is apt to make the low density area narrow on CT, and to prevent the appearance of hemorrhagic infarction.
BACKGROUND: Both pulmonary and systemic circulation must be maintained by a single pump in Fontan circulation. This unique property of Fontan circulation may be related to decreased exercise tolerance or increased instantaneous postoperative mortality rate, often observed in patients with this circulation. To better understand Fontan physiology, the present study theoretically investigated cardiac performance of Fontan circulation by using ventricular-vascular coupling framework analysis. METHODS: End-systolic volume elastance (Ees), as a chamber contractile property, and effective arterial elastance (Ea), a lumped measure of ventricular afterload, were estimated both in normal left ventricular systemic circulation and in Fontan circulation. RESULTS: End-systolic volume elastance was decreased and Ea was increased in Fontan circulation. Both ventricular external stroke work (SW) and mechanical efficiency (EFF) under Fontan circulation were lower compared with those under normal circulation. Furthermore, the Ees-Ea relationship in Fontan circulation predicted limited cardiac reserve in terms of SW and EFF. Such cardiac performance in Fontan circulation stemmed from increased impedance due to the additional connection of the pulmonary vascular bed to the systemic vasculature and from the lack of a compensatory increase in contractility for increased afterload. CONCLUSIONS: Thus, it was inferred that Fontan circulation had intrinsic disadvantages and this may explain, in part, abnormal functional status and decline in survival following this procedure.
PURPOSE: The incidence and biological characteristics of circulating tumor cells in the blood of patients with breast cancer were examined and subgroups were evaluated in the context of systemic treatment and the presence of disseminated tumor cells in bone marrow. EXPERIMENTAL DESIGN: Circulating tumor cells were isolated from the peripheral blood of patients with breast cancer using a gradient system designed for the enrichment of circulating tumor cells (OncoQuick). Circulating tumor cells were identified with the anti-cytokeratin antibody, A45-B/B3. In subsets of patients, expression of the proliferation-associated Ki-67 antigen in circulating tumor cells and the concomitant presence of micrometastases in bone marrow were examined. RESULTS: In patients with primary breast cancer (stage M(0)), circulating tumor cells were detected in 5 of 60 patients (8.3%) after surgery and before initiation of adjuvant chemotherapy; a positive correlation to the presence of disseminated tumor cells in bone marrow was observed (P = 0.030, n = 53). During the course of adjuvant chemotherapy, repeated analysis of 20 M(0) patients revealed the occurrence of circulating tumor cells in 7 of 16 patients that were initially negative. Patients with metastatic disease (stage M(1)) showed circulating tumor cells in 25 of 63 cases (39.7%, P < 0.0001 as compared with M(0) patients), and a positive finding was correlated with elevated concentrations of the serum tumor marker CA15.3 (P = 0.0093). Performing repeated analysis in a subgroup of 25 M(1) patients, circulating tumor cells were found more frequently in patients with progressive disease than in patients with stable disease or remission (87.5% versus 43.8% of patients with circulating tumor cells, respectively; P = 0.047). Independent of the disease-stage, none of the 47 patients examined for the proliferative status of their circulating tumor cells showed coexpression of Ki-67. CONCLUSIONS: Circulating tumor cells seem to be nonproliferating cells that persist during chemotherapy. Circulating tumor cell detection is linked to disease progression and elevated tumor marker concentrations in patients with metastatic breast cancer.
Many of the applications of liposomes drug-delivery systems have been limited by their short circulation half-lives as a result of rapid uptake into the reticuloendothelial (mononuclear phagocyte) system. We have recently described liposomes formulations with long circulation half-lives in mice (Allen, T.M. and Chonn, A. (1987) FEBS Lett. 223, 42-46). A study of the principal factors important to the attainment of liposomes with prolonged circulation half-lives is presented in this manuscript. Liposomes with the longest circulation half-lives, in mice, had compositions which mimicked the outer leaflet of red blood cell membranes (egg phosphatidylcholine/sphingomyelin/cholesterol/ganglioside GM1, molar ratio 1:1:1:0.14). Several other gangliosides and glycolipids were examined, but none could substitute for GM1 in their ability to prolong circulation half-lives. However, other negatively charged lipids with bulky headgroups, i.e., sulfatides and phosphatidylinositol, had some effect in prolonging circulation half-lives, but GM1 was clearly superior in this regard. Bilayer rigidity, imparted by sphingomyelin or other high-phase-transition lipids, acted synergistically with the negatively charged components, especially GM1, in extending circulation times. Circulation half-lives of liposomes increased with decreasing size, but even larger (0.2-0.4 microns) liposomes of the optimum formulations had significantly prolonged half-lives in circulation. Uptake of liposomes into tissues other than liver and spleen increased with increasing circulation times of the liposomes for i.v. and for i.p. injections. Liposomes appeared to move from the circulation into the carcass between 6 and 24 h post-injection. Our ability to achieve significant prolongation in circulation times of liposomes makes possible a number of therapeutic applications of liposomes which, until now, have not been achievable.
OBJECTIVE: We have recently shown that a considerable amount of pro-inflammatory cytokines is released during pulmonary passage after aortic declamping in patients undergoing coronary artery bypass grafting. The present study was performed to investigate whether bilateral extracorporeal circulation with the lungs as oxygenators can reduce the inflammatory responses of the lungs. METHODS: Eighteen consecutive patients undergoing coronary artery bypass grafting were randomly assigned to routine extracorporeal circulation with cannulation of right atrium and aorta (routine circulation, ten patients) or to a bilateral extracorporeal circulation with additional cannulation of left atrium and pulmonary artery (bilateral circulation, eight patients). Blood was simultaneously drawn from right atrium and pulmonary vein at 1, 10 and 20 min reperfusion. The levels of interleukin (IL)-6 and IL-8 and the adhesion molecules CD41 and CD62 on platelets and CD11b and CD41 on leukocytes were determined. Because of considerable interindividual scatter, the pulmonary venous levels are normalized to percent of the respective right atrial value at each time point. RESULTS: At 1 min reperfusion pulmonary venous levels of IL-6 and IL-8 in routine circulation were +44+/-15% and +43+/-28% of the respective right atrial values. The respective values in bilateral circulation were -3+/-4% and -6+/-7% (P=0.02 and P=0.05 vs. respective right atrium). Similar increments were found after 10 and 20 min. Platelet-monocyte coaggregates were retained during pulmonary passage at 1 min reperfusion in routine circulation (-21+/-6%), but washed out in bilateral circulation (+5+/-8%, P=0. 007). At 20 min reperfusion, activated polymorphonuclear neutrophils (PMN) were retained in routine circulation (-16+/-9%) but washed out in bilateral circulation (+19+/-29%, P=0.05; all data given as mean+/-SEM). CONCLUSIONS: Bilateral extracorporeal circulation without an artificial oxygenator significantly reduces the inflammatory responses during pulmonary passage after aortic declamping.
Non pulsatile circulation is commonly applied to clinical cardiopulmonary bypass or circulatory assist. However, influences of non pulsatile circulation on sympathetic nerve activity, which plays an important role in circulatory control, have not been elucidated. In this study the renal sympathetic nerve activity (RSNA) was recorded for the first time in goats, whose heart rate and size are similar to humans', and the difference during pulsatile and non pulsatile circulation was evaluated. Total left heart bypass was instituted in eight adult goats under general anesthesia. A pneumatic pulsatile pump and a centrifugal non pulsatile pump were incorporated in parallel so that pulsatile circulation and non pulsatile circulation could be instantly converted to the other. The pumping rate was set at 90/min regardless of the native heart rate during pulsatile circulation and the mean aortic pressure was maintained constant at the conversion of circulatory mode. The original signals of RSNA were integrated and defined as the mean RSNA. The mean RSNA and the mean aortic pressure were averaged every 30 sec and quantified during pulsatile circulation and non pulsatile circulation. The pulse synchronized burst of RSNA during pulsatile circulation immediately disappeared and the mean RSNA significantly increased up to 120% of pre depulsation level after changing the circulatory mode to non pulsatile circulation. Reverse conversion of circulatory mode from non pulsatile circulation to pulsatile circulation decreased the mean RSNA to 79%. The results suggest that vasotonus may be affected in its periodicity as well as its quantity by the loss of pulsation during the initial phase after depulsation.
The present investigation was designed to examine the effect of four atrial peptide hormones with vasodilatory properties on the circulating immunoreactive (ir) levels of the vasoconstrictive peptide endothelin (ET) in 36 healthy human subjects. Circulating levels of human ET and cyclic guanosine monophosphate ([cGMP], a potential mediator of the effects of atrial peptides), were measured every 30 minutes during 1-hour preinfusion, 1-hour infusion, and 3-hour postinfusion periods. Atrial natriuretic factor ([ANF] amino acid (aa) 99 to 126 of the 126-aa ANF prohormone) and kaliuretic peptide (aa 79 to 98 of this same prohormone) significantly (P<.05) decreased circulating ET concentrations. Kaliuretic peptide effects were early and ANF effects were delayed until kaliuretic peptide effects began to wane. Long-acting natriuretic peptide (LANP), consisting of aa 1 to 30 of the ANF prohormone, on the other hand, significantly (P<.05) increased ET circulating concentrations during a 1-hour infusion period. The increase in ET in the circulation secondary to LANP became nonsignificant, although it was still elevated, within 30 minutes of ceasing LANP infusion. Vessel dilator, consisting of aa 31 to 67 of the ANF prohormone, and infusion of vehicle alone did not significantly change circulating levels of ET during the 5 hours of this investigation. ANF infusion increased plasma cGMP sevenfold, but plasma cGMP had decreased to only onefold above normal during the period that ANF had an effect on circulating ET levels. There was not any significant increase or decrease in plasma cGMP concentrations secondary to the other atrial peptide hormones. These data suggest that kaliuretic peptide and ANF negatively modulate circulating ET concentrations, while LANP, which is released simultaneously with ANF in response to physiologic stimuli, positively modulates circulating ET concentrations to help maintain circulating ET within a narrow normal range. The data from the present investigation would further suggest that circulating cGMP levels do not mediate the various atrial peptide effects on circulating ET levels.
We have developed an apparatus utilizing laser speckle phenomenon which can measure the peripheral circulation in the iris, choroid, retina and optic nerve head (ONH) and blood velocity through retinal vessels in the living eye non-invasively and quantitatively. A blue-component argon laser (wavelength 488 nm) was used for measurement of peripheral circulation in the retina and a diode laser (wavelength 808 nm) for measurements of peripheral circulation in the iris, posterior choroid and ONH, and measurement of centerline blood velocity through retinal vessels. A fundus camera (TRC-WT 3, Topcon) was equipped with a laser source and an image sensor where the speckle pattern from the fundus appears, and the data were analyzed with a personal computer to give a normalized blur (NB) value or a square blur rate (SBR) value, both quantitative indices of blood velocity. The NB value, whose computation requires much less time, was adopted to evaluate peripheral circulation because of non-linear correlation between the NB and actual blood velocity in the range above 20 mm/sec. The SBR value, whose computation requires a longer time, was adopted for measurement of blood velocity through retinal vessels. Measurement field in the living eye was 1.06 x 1.06 mm at its maximum and reproducibility index of the in vivo measurement in the rabbit iris, choroid, retina, and ONH was approximately 10%. When blood flow was changed by intraocular pressure (IOP) change in rabbit eyes, NB values obtained from the iris, choroid, and retina showed a significant correlation with the blood flow simultaneously determined with the colored microsphere technique in the same eye, and the NB obtained from the ONH also correlated with the blood flow determined with the H2 gas clearance method. Stepwise reduction in the ocular perfusion pressure (OPP) by stepwise increment of IOP resulted in proportional reduction in the iris- and choroid-NB. On the other hand, the retina- or ONH-NB remained almost unaltered at OPP levels above 50 mmHg, and decreased along with OPP at levels less than 50 mmHg. By monitoring NB values for 2 hours, presence or absence of autoregulatory mechanism against OPP change in the choroidal and ONH circulation was studied in rabbits. Throughout the experimental period of 2 hours, the choroidal NB was changed along with the OPP change, suggesting absence of blood flow autoregulation in this tissue. In the ONH, however, the NB returned to the baseline after its transient increase or decrease when the OPP was continuously increased or decreased, showing the presence of an autoregulatory mechanism in the ONH circulation. However, the time course of the NB resumption depended on the extent of OPP change. These results indicated that the laser speckle method can be useful in investigating the autoregulatory mechanism and processes of peripheral circulation in ocular tissues. Unilateral instillation of drugs with vasodilative activity (ifenprodil, betaxolol or nipradilol) in rabbit eyes significantly increased ONH and/or choroidal circulation. The extent in change in the ONH and/or choroidal circulation correlated with the number of doses, but not with the extent of IOP reduction, which suggested that the observed effects were attributable to the drug which penetrated locally. Intravenous administration of a Ca(2+)-antagonist (nicardipine, nilvadipine or pranidipine) significantly increased choroidal or retinal circulation in rabbits. The ONH circulation, however, was not affected by nicardipine, but affected by nilvadipine or pranidipine. Given the same effect on the ONH circulation, systemic hypotensive effect was stronger in pranidipine than in nilvadipine, which suggested that nilvadipine can be used in patients with ocular circulatory insufficiency. A modification of the laser speckle apparatus used for animal experiments was devised so that the NB or SBR values could be measured in human eyes every 0.12 sec on a real-time basis. (ABSTRACT TRUN
The functional significance of the coronary collateral circulation remains controversial. It has been suggested that collateral circulation possibly helps prevent myocardial ischemia. Seventeen target lesions in 15 patients were studied to determine the relationship between the extent of the coronary collateral circulation and the degree of ventricular dysfunction during percutaneous transluminal coronary angioplasty (PTCA). During the first balloon inflation, diastolic indices such as left ventricular end-diastolic pressure, max negative dP/dt and the time constant of early relaxation were measured immediately before and at 60 sec following balloon inflation. During the second inflation, the contralateral and ipsilateral collateral circulations were evaluated. The latter was graded as follows: 0 = none; I = filling of side branches only; II = partial filling of the epicardial segment; and III = complete filling of the epicardial segment. Following balloon inflation, a significant increase was noted in the time constant of early relaxation in patients with grade 0 collateral circulation (40 +/- 7 to 47 +/- 7 msec: p < 0.01) and grade II collateral circulation (52 +/- 12 to 56 +/- 13 msec: p < 0.05). The percent increase in the time constant of early relaxation of patients with grade 0 and I collateral circulations exceeded that of patients with grade II (p < 0.05) or grade III collateral circulation (p < 0.05). Left ventricular end-diastolic pressure was elevated in all groups during PTCA. There was no significant difference in the percent increase of left ventricular end-diastolic pressure (LVEDP) between the 4 groups. However, LVEDP before PTCA was higher in patients with grade III collateral circulation than in patients in the other groups. Max negative dP/dt did not change significantly in any group. In conclusion, collateral circulation helps prevent myocardial ischemia during acute coronary occlusion, which is most precisely shown by the time constant of early relaxation. The degree of this protective function of collateral circulation seems to vary.
BACKGROUND: Clinical effects of internal carotid artery (ICA) occlusion may range from the absolute absence of symptoms to lethal hemispheric stroke. In this paper symptoms of patients with ICA occlusion have been related to the development of collateral circulation, different types of developed collateral circulation have been assessed, and the degree of sensitivity and specificity of duplex scan has been appraised. METHODS: Forty-eight patients with ICA occlusion or subocclusion, 24 males and 24 females, aged between 50 and 83 years (67.7+/-7.15), underwent duplex scan and magnetic resonance (MR) angiography. Nineteen patients were completely asymptomatic, 20 patients showed permanent neurological symptoms and 9 patients had shown transient symptoms. RESULTS: Twelve patients (25%) did not show any collateral circulation, 29 patients (60%) showed collateral circulation through homolateral external carotid artery branches and 7 patients (15%) showed collateral circulation through other circuits. Of the 20 patients with permanent symptoms only 8 showed collateral circulation. On the contrary, all the 19 asymptomatic patients and the 9 patients with transient symptoms showed collateral circulation. Eventually, duplex scan showed 78% sensitivity, 100%, specificity and 83% diagnostic accuracy. CONCLUSIONS: Our data show: 1) a clear-cut prevalence of collateral circulation through homolateral external carotid artery branches with respect to other possible collateral circulation; 2) an inverse relationship between the development of collateral circulation and the appearance of permanent symptoms; 3) a good diagnostic accuracy of duplex scan in revealing collateral circulation in the case of ICA occlusion.
It is becoming increasingly apparent that certain forms of acute and chronic inflammation are associated with enhanced production of nitric oxide (NO). Although substantial information has been obtained describing the regulation of NO synthase (NOS) in macrophages, little information is available regarding the biochemistry and molecular biology of NOS in circulating vs. extravasated polymorphonuclear leukocytes (PMNs). The objective of this study was to characterize the molecular and biochemical properties of the inducible NO synthase (iNOS) in circulating vs. extravasated rat and human PMNs. Circulating rat and human PMNs were purified from peripheral blood and extravasated PMNs were elicited in rats by intraperitoneal injection of 1% oyster glycogen or in humans by peritoneal dialysis of patients with peritonitis. Inducible NOS mRNA from circulating and elicited PMNs was quantified using slot blot hybridization analysis with a cDNA probe specific for iNOS. iNOS protein was identified using Western immunoblot analysis, and NOS activity was quantified by measuring the NG-monomethyl-L-arginine (L-NMMA)-inhibitable conversion of 14C-labeled L-arginine to L-[14C]citrulline. In a separate series of experiments, circulating or extravasated PMNs were cultured for 4 h and the accumulation of L-NMMA-inhibitable nitrite (NO2-) in the supernatant was determined and used as a measure of NO production in vitro. We found that circulating PMNs (rat or human) contained no iNOS mRNA, protein, or enzymatic activity. Furthermore, circulating rat or human PMNs (2 x 10(6) cells/well) were unable to generate significant amounts of NO2- when cultured for 4 h in vitro. In contrast, iNOS mRNA levels in 4- and 6-h elicited rat PMNs increased 21- and 42-fold, respectively, when compared with circulating cells. Western blot analysis revealed the presence of iNOS protein in the elicited rat PMNs and iNOS enzymatic activity increased from normally undetectable levels in circulating rat PMNs to 81 and 285 pmol/min/mg for the 4- and 6-h elicited rat PMNs, respectively. Approximately 20-30% of the total iNOS activity was Ca(2+)-dependent. Nitrite formation by elicited rat PMNs in the absence of any exogenous stimuli increased from normally undetectable amounts for circulating PMNs to approximately 8 and 11 microM/10(6) cells for the 4- and 6-h elicited PMNs, respectively. Highly enriched preparations of extravasated human PMNs contained neither message, protein nor iNOS enzymatic activity. Taken together our data demonstrate that inflammation-induced extravasation of rat PMNs upregulates the transcription and translation of iNOS in a time-dependent fashion and that 20-30% of the total inducible NOS is Ca(2+)-dependent. In contrast, neither circulating nor extravasated human PMNs contained iNOS message, protein, or enzymatic activity. These data suggest that the human PMN iNOS gene is under very different regulation than is the rat gene.