Dynamics of atrial peptide secretion in the coronary circulation of the conscious dog.

The secretion of atrial natriuretic peptide by the heart is not simply the arterial-coronary sinus concentration difference times coronary blood flow, because only a small fraction of total coronary blood flow passes through the atria. We measured coronary sinus and arterial plasma atrial natriuretic factor (ANF) concentrations and blood flow to each part of the heart using the radioactive microsphere technique. Before acute volume expansion, the arterial-coronary sinus ANF difference was 305 +/- 23 pg/ml and rose to 1,009 +/- 220 pg/ml during volume expansion, whereas total coronary blood flow rose from 167 to 465 ml/min. Atrial blood flow rose from 2.9% to 4.6% of total coronary blood flow during volume expansion. ANF secretion rate increased from 51 to 469 ng/min. When divided by atrial weight, ANF secretion rate increased from 4.0 +/- 0.3 to 56 +/- 12 ng/min/g atrial tissue-in other words, from 0.3% to 3.7% of tissue ANF content each minute. Dividing by atrial blood flow indicated that the concentration of ANF leaving atrial tissue was 10,000 to 29,651 pg/ml, and the additional secretion of ANF was determined by the increase in coronary blood flow. Therefore, at least two mechanisms are responsible for altering coronary sinus ANF and circulating ANF: the release rate from atrial myocytes and the washout via changes in atrial blood flow.

Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. III. Long-term changes and their modification by platelet inhibition with aspirin and dipyridamole.

The objectives of this study were to elucidate the long-term influence on vein bypass grafts of platelet inhibition and its late discontinuation. Cephalic vein grafts were interposed bilaterally in the femoral arteries of stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. Fifteen animals were divided into three groups of five animals each. Group I received no medications and served as a control group. Group II received for the full duration of the study a combination of aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Group III received the same regimen of platelet inhibition as in group II during the first 9 months, but were not treated during the subsequent 9-month interval. Grafts were excised for analysis from groups I and II at both 9 and 18 months and from group III at 18 months. Cholesterol content in group I grafts was 470 +/- 89 micrograms/100 mg at 9 months and 388 +/- 127 micrograms/100 mg at 18 months. In group II grafts, cholesterol content was 208 +/- 72 micrograms/100 mg at 9 months (p less than 0.001 compared with group I) and 266 +/- 84 micrograms/100 mg at 18 months. In group III grafts, cholesterol content was 249 +/- 71 micrograms/100 mg at 18 months. Differences in cholesterol content among the three groups of grafts at 18 months were not found to be statistically significant. Stepwise regression analysis at 18 months showed that cholesterol content was best predicted by medial fibrosis (r2 = 0.66) followed by abundance of foam cells (increase in r2 = 0.26) in group I, by fibrin in group II (r2 = 0.63), and by prevalence of macrophages in group III (r2 = 0.74). In all groups, platelets, fibrin, and polymorphonuclear leukocytes were less abundant than they had been at 3 months. Cross-sectional area occupied by the intima was not influenced by platelet inhibition.

Evidence for lipid peroxidation in atherosclerosis.

Lipid peroxidation may play a significant role in the initiation and progression of atherosclerotic plaque. Freshly harvested normal and atherosclerotic human aortic tissue, coronary arteries and explanted vein grafts were snap frozen at -70 degrees C. Folch reagent (chloroform-methanol 2:1, v/v) was used to extract lipids from the homogenates. These extracts were assayed for cholesterol, phospholipid and triglyceride content. Lipid peroxide complexes in vessels were measured fluorometrically. Atherosclerotic plaque from patients with aortic aneurysmal and occlusive disease and coronary artery disease contained significantly greater amounts of cholesterol (15.54 +/- 9.71 vs 3.39 +/- 1.14 mg/g tissue) than controls (p less than 0.01). Lipid peroxide fluorochromes were similarly elevated in all atherosclerotic tissue (4.159 +/- 1.065 vs 3.087 +/- 0.497 fluoro units/g tissue) compared to control (p less than 0.01) with significant elevations in saphenous vein grafts and occlusive aortic disease. Although lipid peroxidation and lipid accumulation occur in close association in atherosclerotic plaque, the role of lipid peroxides in the pathogenesis of atherosclerosis remains to be determined.

Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. II. Modification of early changes by platelet inhibition with aspirin and dipyridamole.

The objective of this study was to determine the early influence of platelet inhibition on the histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. Cephalic vein grafts were interposed bilaterally in the femoral arteries of 15 stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. All animals received in combination aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Grafts were excised from five animals for analysis on each of postoperative days 3, 7, 14, 30, 60, and 90. In animals subjected to platelet inhibition, cholesterol content in the graft was 170 +/- 52 micrograms/100 mg at 90 days, 205% of the level in ungrafted vein (p less than 0.01). This change was small in comparison with the increase to 686% of ungrafted vein observed in our study of control animals. In stepwise regression analysis, cholesterol content of grafts was best predicted by prevalence of foam cells (r2 = 0.82), and the proportion of intima as a fraction of total wall area was best predicted by the presence of macrophages (r2 = 0.69). Platelet inhibition did not decrease the extent of intimal hyperplasia. The prevalence of adherent platelets (r = -0.72) and the amount of fibrin (r = -0.78) correlated inversely with the amount of endothelium present during the first 14 days. The strength of these correlations declined with time, despite persistent lack of endothelium in some areas. Medial fibrosis occurred to the same extent as in control grafts, as did the early appearance of platelet factor VIII and fibronectin and the lack of vasa vasorum at 3 days followed by reappearance at 7 days. These data demonstrate that platelet inhibition dramatically reduces lipid uptake by grafts in the first 90 days but has less influence over histologic or morphometric changes.

Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. I. Sequential changes within the first three months.

The objective of this study was to define the histologic and morphometric evolution that accompanies the increase in cholesterol content of vein bypass grafts in a nonhuman primate model. Cephalic vein grafts were interposed bilaterally in the femoral arteries of 15 stump-tailed macaque monkeys (Macaca arctoides), which were fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. Grafts were excised from five animals for analysis on each of postoperative days 3, 7, 14, 30, 60, and 90. Cholesterol content increased from 69 +/- 24 micrograms/100 mg (mean +/- standard deviation) in ungrafted vein to 473 +/- 122 micrograms/100 mg in grafts 90 days after implantation (p less than 0.05). By stepwise regression analysis, cholesterol content was best predicted by abundance of foam cells (r2 = 0.82). Intima comprised 13% +/- 5% of the total cross-sectional area of the wall in ungrafted vein and 59% +/- 11% at day 90 (p less than 0.001). With cholesterol content excluded from the stepwise regression, intimal area was best predicted by the presence of foam cells (r2 = 0.39). There was consistently an increase in the prevalence of polymorphonuclear leukocytes on the luminal surface and in both the intima and media during the first 14 days after grafting. Vasa vasorum, which were always present in ungrafted vein, were sparse at 3 days but reappeared by day 7. Medial fibrosis occurred in grafts, and in the 30- to 90-day interval it was directly correlated with the number of adventitial vasa vasorum present (r = 0.64, p less than 0.05). Immunohistochemistry revealed prominent staining for both platelet factor VIII and fibronectin during the first month, with a gradual decline in staining intensity thereafter. The evolution of changes in vein bypass grafts documented in this report are in general agreement with graft changes observed in humans and support the validity of our model in evaluating the histologic correlates of increased graft cholesterol content.

Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients.

The aim of this study was to determine the extent of accumulation of lipoprotein(a) [Lp(a)] in human arterial wall and to define its potential role in atherogenesis. Biopsies routinely taken from the ascending aorta of 107 patients undergoing aortocoronary bypass surgery were analyzed for lipid and lipoprotein parameters, which were then correlated to serum values. A significant positive correlation was established between serum Lp(a) and arterial wall apolipoprotein (apo)(a) by enzyme-linked immunosorbent assay. High serum Lp(a) also led to a significant increase of apo B in the arterial wall. No significant correlation was found between apo B in serum and aortic tissue. Apo B was found to be partially linked to apo(a) in the aortic extract. Furthermore, apo(a) was found to be intact, as determined by its molecular weight in sodium dodecyl sulfate electrophoresis. This technique also revealed that the apo(a) isoform pattern of aortic homogenate was comparable to the individual serum pattern. Immunohistochemical methods demonstrated a striking colocalization of apo(a) and apo B in the arterial wall, predominantly located extracellularly. Both proteins were increased in atherosclerotic plaques. With density gradient ultracentrifugation, Lp(a)-like particles could be isolated from plaque tissue. This initial study showed that Lp(a) accumulates in the arterial wall, partly in the form of lipoprotein-like particles, therefore contributing to plaque formation and coronary heart disease.

The activity of diagnostic enzymes and the concentration of lipids in the blood vessels of cattle.

Blood vessel walls are shown to contain creatine phosphokinase, lactate dehydrogenase, gamma glutamyl transpeptidase and aspartate transaminase activity. The activity of these enzymes in the serum may be enhanced by leakage from damaged blood vessels. The activity of the enzymes alanine transaminase and alkaline phosphatase as well as the content of triglycerides, cholesterol and lipoproteins are very low in the vascular tissue and are unlikely to be of diagnostic value in vascular tissue injury.

Characterization of histamine receptors in isolated rabbit veins.

Veins were isolated from 16 sites of the rabbit venous tree and responses to histamine and histamine receptor agonists were studied to characterize the histamine receptors. Isometric contraction and relaxation of ring segment preparations were recorded. Histamine produced concentration-dependent contractions in all veins in the resting state. Both the maximum response and pD2 value varied remarkably from vein to vein and regional differences in sensitivities to histamine varied considerably from previous findings in dog veins. Also in the precontracted state with a vasoconstricting agent, histamine predominantly contracted the veins. The contractile responses to histamine, in both resting and precontracted states, were antagonized competitively by the histamine H1-receptor antagonist, mepyramine. On the other hand, histamine relaxed the precontracted veins, in the presence of mepyramine. Selective H2-receptor agonists, dimaprit and impromidine, relaxed the precontracted veins even in the absence of mepyramine. These responses to histamine were antagonized competitively by the H2-receptor antagonist, cimetidine or ranitidine. The present study provides quantitative and systematic data regarding histamine receptors in rabbit veins. We propose that: 1) there are both vasoconstrictor H1-receptors and vasodilator H2-receptors, 2) histamine generally contracts rabbit veins through predominant H1-receptors and that 3) the H2-receptor-mediated relaxation does not depend on the presence of the endothelium.

[Quantitative determination of tissue-type plasminogen activator in varicose soleus veins]. / Détermination quantitative de l'activateur du plasminogène tissulaire dans les veines soléaires variqueuses.

Any thrombotic affection can involve the deep veins as well as the superficial veins of the calf. It is considered that venous thrombosis may be a result of low concentrations of the activator of plasminogen levels in the vein wall, which produces a mediocre fibrinolytic response. The concentrations of the activator of plasminogen in these veins are little knows. Immediately after amputation, for pain in the decubitus position, samples of the soleus vein (N = 9) and long saphenous vein (LSV; N = 9) were removed and frozen in liquid nitrogen. In 6 limbs operated for varicose veins, samples of the vein in the calf (VC; N = 6) were removed and frozen. As a control, we examined samples of normal veins removed from the groin of patients undergoing hernia repairs. The quantitative determination of the activator of plasminogen was achieved thanks to a homogenate technique, and the results were expressed in taps by the minute by a tissue microgram. The median activity and the range of results were: LSV 1675 (777-8119); soleus vein 6795 (2232-21 570); CV 2356 (676-4099); inguinal veins 11 221 (6717-13 410). The low concentration of activator of plasminogen in the calf veins may contribute to a mediocre fibrinolytic response in these veins. This is not likely to be the case in the soleus veins. The results may indicate a different thrombotic mechanism in the two types of veins.

Distribution of von Willebrand factor in porcine intima varies with blood vessel type and location.

The von Willebrand factor (vWF) has been generally accepted as a marker for endothelial cells. In a systematic immunolocalization study of porcine blood vessels that used indirect immunofluorescence with a monospecific polyclonal anti-vWF and two monoclonal anti-vWFs, we observed that vWF is not universally distributed in intact, fresh endothelia. vWF is consistently localized in veins, with the exception of the pulmonic vein. In arteries, vWF is generally absent except for areas of the distal abdominal aorta, the vaso vasorum of the thoracic aorta, and the pulmonic artery. We conclude that there are regional differences in the distribution of vWF in the various endothelial beds of pigs.

Maturational changes in the pharmacological characteristics and actomyosin content of canine arterial and venous tissue.

The purpose of this study was to compare the pharmacological characteristics and actomyosin content of arterial and venous tissue at different times during development. Rings of arteries (femoral, renal, carotid, pulmonary) and veins (saphenous, pulmonary, jugular) were obtained from 1 wk, 1 month, and adult dogs, mounted at their optimal length for force development and the contractile response to potassium chloride and phenylephrine determined. The strain at optimal length was less at all ages in pulmonary artery and pulmonary and jugular veins than in other vessels. All vessels exhibited an increase in maximum contractile response with development but the increase was greater for phenylephrine. In general, the magnitude of the maximum response of the jugular and pulmonary veins and pulmonary artery was less than other vessels at all ages. The sensitivity (half maximum response) either increased or was unchanged in arteries with development, while in the veins it either decreased or was unchanged. The relaxant effects of verapamil and isoproterenol were determined on potassium chloride contracted vessels. Arterial tissue was minimally responsive to isoproterenol at all ages while venous tissue either increased its responsiveness (saphenous, pulmonary) with development or remained highly responsive (jugular). Verapamil, unlike isoproterenol, was an effective relaxant of all vessels. The actomyosin content (mg/mm) of femoral and renal arteries and saphenous and jugular veins increased with development but this increase was accompanied by a parallel increase in total protein so that the ratio (actomyosin/total protein) was unchanged. In jugular veins from adult dogs this ratio was smaller than in arterial tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Norepinephrine-sensitive, phenoxybenzamine-resistant receptor sites associated with contraction in rabbit arterial but not venous smooth muscle: possible role in adrenergic neurotransmission.

The possibility that not all contractions of rabbit blood vessels to norepinephrine (NE) are mediated through alpha adrenoceptors sensitive to phenoxybenzamine (PBZ) was investigated. Dose-response curves (DRCs) to NE were made in the absence and presence of PBZ pretreatment which minimized the contribution of alpha adrenoceptors. In all arteries studied (saphenous, renal, femoral and central ear arteries), after PBZ-treatment, NE produced biphasic DRCs. The initial component of these DRCs corresponded to doses of NE which in the absence of PBZ were supramaximal. Under conditions of our experimentation the plateau-phase usually occurred at between 5 and 40% of the pre-PBZ maximal response to NE. The second phase occurred with further additions of NE, and achieved a mean of 72 (+/- 4)% of the pre-PBZ maximal contraction to NE. The latter component presumably represented contractions mediated through low-affinity sites for NE which were insensitive to doses of PBZ sufficient to alkylate alpha adrenoceptors. In veins (saphenous and inferior vena cava), we found no evidence for such sites. Our results are discussed in light of current ideas of adrenergic neurotransmission in vascular smooth muscle as proposed by Hirst and Neild (1980a) and others who suggest that response to high concentrations of neuronally released NE occur through PBZ-resistant receptors termed gamma adrenoceptors located exclusively at the postsynaptic membrane. We were able to demonstrate PBZ-resistant, low-affinity sites for NE contractions in the femoral artery, a vessel with very sparse adrenergic innervation, and conclude that such sites for NE are present in a number of arteries (and not veins) irrespective of their innervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous venous oximetry in surgical patients.

A prospective study was performed to evaluate the efficacy of continuous venous oximetry to supplement traditional hemodynamic monitoring in 39 critically ill surgical patients. There was no statistically significant difference in SvO2 between the continuous in vivo values and in vitro values (0.694 +/- 0.095 vs. 0.698 +/- 0.108). There was no statistically significant correlation between continuously measured SvO2 and PaO2 (r = 0.09, p greater than 0.5), SaO2 (r = 0.08, p greater than 0.5), or oxygen consumption (r = 0.46, p greater than 0.5). There was a slight but statistically significant correlation between continuously measured SvO2 and cardiac output (r = 0.40, p less than 0.025) and oxygen delivery (r = 0.49, p less than 0.005). There was a highly significant correlation between continuously measured SvO2 and oxygen utilization coefficient (r = -0.96, p less than 0.001). Continuously measured SvO2 is a reliable predictor of SvO2 measured intermittently by in vitro methods. In critically ill surgical patients, SvO2 does not correlate highly with the individual determinants of oxygen transport but rather correlates with the oxygen utilization coefficient and therefore reflects the overall balance between oxygen consumption and delivery.

Adrenergic innervation and neurogenic response in large and small arteries and veins from the rat.

A combined morphological and physiological analysis of the properties of the adrenergic vasoconstrictor innervation was carried out in the splanchnic vasculature in the rat. Three generations of vessels were studied: (1) the abdominal aorta and the caval vein; (2) the superior mesenteric artery and vein; (3) 200 microns branches of the superior mesenteric artery and their parallelling veins. The adrenergic innervation was visualized by the Hillarp-Falck fluorescence technique, and by the immunohistochemical localization of immunoreactivity to tyrosine hydroxylase and dopamine-beta-hydroxylase. Determination of responses to applied noradrenaline, to transmural nerve stimulation and to direct activation of the muscle was made on ring preparations mounted in a myograph. All vessels were found to be innervated at the adventitio-medial border by noradrenergic nerves with varying density; the small arteries had the highest nerve density, the abdominal aorta was least innervated. When related to the maximal isometric response to applied noradrenaline, the maximal neurogenic response parallelled the density of the adrenergic innervation. Variations in frequency for half-maximal response among the vessels could not, however, be ascribed to innervation properties only. The constriction under isotonic conditions amounted to 20% of the initial circumference in the aorta, and to 30% in the small arteries and veins. The relation between response to applied noradrenaline and to nerve stimulation was similar for isometric and isotonic responses. In the smaller veins, a beta-receptor-mediated decline in the response to applied noradrenaline was seen. This decline was much less pronounced in neurogenic responses. The results indicate a gradation from proximal to peripheral arteries towards denser innervation and greater neurogenic responses. On the venous side only minor differences were found.