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Objective: Aprotinin reduces postoperative bleeding and the need for transfusion after cardiopulmonary bypass. The current clinical concern about aprotinin is that it may increase the incidence of postoperative graft thrombosis and thromboembolic phenomena. The fact that the mechanism of action of aprotinin is not completely elucidated and that its effects on the vascular reactivity of bypass conduits are unknown raise doubts regarding its safety. In an attempt to clarify these issues we investigated the vascular reactivity of the human saphenous vein and internal thoracic artery to a range of vasoconstrictor agents in the presence or absence of aprotinin., Methods: Human saphenous vein was obtained from 24 patients and internal thoracic artery from 7 patients undergoing coronary artery bypass. Vessels were set up in organ baths to record changes in vessel wall tension., Results: Endothelium-dependent relaxations to acetylcholine in saphenous vein rings were unaffected after aprotinin treatment. Contractions to the thromboxane analog U46619 were significantly attenuated after aprotinin treatment in the saphenous vein. Maximum responses were reduced from control values of 88 +/- 7.5 mN to 49.3 +/- 4.8 mN with 1 mumol/L doses of aprotinin (p < 0.05) and 36.6 +/- 4.8 mN with 10 mumol/L doses of 5-hyroxytryptamine or noradrenaline after aprotinin incubations. Furthermore, contractions to U46619 in the internal thoracic artery were unaffected by aprotinin., Conclusion: Our data show that there is a preservation of endothelium-dependent responses to acetylcholine and a reduced U46619 vasoconstrictor action on the saphenous vein after aprotinin treatment. Thus the direct effect of aprotinin on the vessel wall could counteract the potential effect of its prothrombotic action on graft patency.

The purpose of this paper is to examine the effects of residual stresses and strains in the oscillating arteries on the stress distribution in the vascular wall. We employ a static theory of large elastic deformations for orthotropic material (Chuong and Fung, 1986, J. biomech. Engng 108, 189-192) with the acceleration term added to make the theory dynamic. We use the static elastic parameters of residual stresses in our analysis because the dynamic parameters are not available in the literature. Our analysis reveals that the effect of considering the residual stresses is to decrease the very large circumferential stresses at the inner wall by 62% and reduces the stress gradient through the arterial wall by 94% compared to the case when residual stresses are ignored. Thus, because the arteries do contain residual stresses, the consequent lower stresses at the inner wall and the reduced stress gradient may reduce the progression of atheroma. Our computations show that the stress gradients do not depend on the heart rate.

Objective: The purpose of this study was to evaluate in dogs the effect of blood flow alteration on caliber and morphology of in situ internal thoracic arteries., Methods: Six dogs underwent creation of a unilateral distal arteriovenous fistula between the internal thoracic artery and vein at the sixth rib to create high flow, and in six others the internal thoracic artery was unilaterally skeletonized and dissected. For both groups the contralateral internal thoracic artery served as the control; sides were alternated among cases. Blood flow was measured for shear stress calculation before and after surgical alteration. After 2 months, internal thoracic arteries were harvested with the entire anterior chest plate, which was dynamically inflated and fixed with 10% formalin at a controlled pressure of 120 mm Hg after angiography had been done at the same pressure. The luminal diameters were then measured at eight levels on the angiograms. Arterial tissue samples were taken at three levels and embedded, sectioned, and treated with hematoxylin-eosin and Verhoeff-van Gieson stains. Digital imaging analysis was used for quantitative morphometric studies., Results: All fistulas remained patent. In comparison with control arteries, high-flow internal thoracic arteries dilated and low-flow internal thoracic arteries narrowed, which was associated with significant change in shear stress for both groups. There were no substantial structural changes in the walls of either group., Conclusion: In the dog, the luminal diameter of the internal thoracic artery responds to altered blood flow without intimal thickening or other undesirable wall changes.

In the present study, the tissue content and functional effects of endothelin-1 and endothelin-3 were examined in human vessels of importance in coronary bypass operations. Human coronary arteries (i.e., the left anterior descending coronary artery) were obtained from eight cardiac valve donors within 6 hours after death, pulmonary arteries were perioperatively obtained from 15 patients operated on because of lung tumors, and internal thoracic arteries and great saphenous and cephalic veins were obtained at coronary bypass operations from a total of 28 patients. Endothelin-1 and endothelin-3 content was quantified by radioimmunoassay. For functional experiments, the vessels were mounted in organ baths for recordings of isometric contractions in response to endothelin-1, endothelin-3, and the endothelinA-receptor agonist sarafotoxin 6c. In all vessels investigated, the endothelin-1 content was higher than that of endothelin-3. The highest levels were found in the left anterior descending coronary artery, followed in declining order by the internal thoracic artery, pulmonary artery, saphenous vein, and cephalic vein. Endothelin-1 contracted all vessels in a concentration-dependent fashion. This effect was enhanced in the left anterior descending and internal thoracic arteries by inhibition of nitric oxide and prostaglandin formation. The contractile effect was attenuated in a concentration-dependent fashion in all vessels by incubation with the endothelinA-receptor blocker BQ-123. Furthermore, contractions evoked by endothelin-1 in the left anterior descending coronary and pulmonary arteries were antagonized by the combined endothelinA- and endothelinB-receptor blocker bosentan. Endothelin-3 contracted the left anterior descending coronary and pulmonary arteries and the saphenous vein, but not the internal thoracic artery, in a BQ-123-sensitive fashion. However, after inhibition with nitric oxide or prostaglandin, endothelin-3 also contracted the internal thoracic artery, and the response in the left anterior descending coronary artery was enhanced. Sarafotoxin 6c evoked a BQ-123-sensitive contraction of the left anterior descending coronary artery. It is concluded that endothelinA receptors mediate the major portion of the vasoconstriction observed on exposure to endothelin-1, endothelin-3, and sarafotoxin 6c in the left anterior descending coronary, pulmonary, and internal thoracic arteries and the saphenous vein. Furthermore, endothelinB-receptor activation, with subsequent formation of nitric oxide or prostaglandin (or both), counteracts the vasoconstrictor response to endothelin in the left anterior descending coronary and internal thoracic arteries, but not in the pulmonary artery or saphenous vein. The present findings therefore suggest that endothelinA-receptor antagonism might prove beneficial in preventing possible endothelin-induced coronary graft spasm.

Surgeons have limited ability to evaluate intraoperatively the patency of internal thoracic artery graft as a bypass for coronary artery revascularization. We used continuous-wave Doppler ultrasonography to study the velocity of the internal thoracic artery before harvesting and after grafting (scanning probe, 8 MHz). Systolic and diastolic frequency shift (in kilohertz) and systolic frequency/diastolic frequency index were analyzed. Twenty four internal thoracic artery grafts in 15 patients were studied. Fourteen internal thoracic artery grafts were anastomosed to the left anterior descending artery, one to a diagonal artery, and nine to the circumflex artery. The mean systolic frequency before harvesting was 1.19 +/- 0.40 KHz and no significant differences were found between the right and the left internal thoracic artery (right, 1.17 +/- 0.37; left, 1.19 +/- 0.42 KHz). There was a 40% drop in systolic frequency related to the harvesting. Mean systolic frequency decreased after grafting (1.19 +/- 0.40 versus 0.87 +/- 0.32 KHz; p < 0.01) whereas mean diastolic frequency doubled (0.32 +/- 0.12 versus 0.83 +/- 0.4 KHz; p < 0.001) and mean diastolic frequency/systolic frequency index increased from 28% +/- 11% to 101% +/- 39% (p < 0.001), indicating an increased myocardial vascularization during diastole. No significant difference was found between grafted arteries (left anterior descending versus circumflex). All patients had an uneventful postoperative course and no perioperative myocardial infarction was reported. Doppler flow quantification of internal thoracic artery bypasses may give the surgeon an opportunity to evaluate intraoperatively the physiologic features and patency of the internal thoracic artery before and after coronary artery bypasses.

Because of the lack of a sophisticated pump management system, the performance of the Hemopump in patients cannot assessed successfully. To clarify the interrelationship between an intravascular nonpulsatile pump and a pulsating ventricle, an in vitro study was set up under controlled conditions. Before these in vitro experiments, a series of in vivo experiments were performed in sheep using Hp31 cannulae. As anticipated, the resulting pulsatile pump flow was a function of the momentary pressure difference across the pump. This varying pump flow showed a significant flow loop hysteresis, indicating that the pressure difference across the pump is not the only parameter governing momentary pump flow of a rotary pump operating at constant speed in a pulsatile environment. Furthermore, flow in the Hp31 was significantly influenced by the inflow situation, blood supply, size of the ventricular cavity, and shape and position of the inflow cannula within the ventricle. Pulsatile flow conditions with good as well as impaired inflow into the pump were accordingly simulated in vitro to verify the in vivo measurements, to characterize the various inflow conditions, and to discuss methods of improved pump management. As a result of the in vivo and in vitro experiments, one can rely on the measurement of nonpulsatile in vitro flow and pressure differences across the pump to characterize the momentary pump flow for good inflow conditions into the pump. For these situations, the flow hysteresis produced, caused by fluid inertia within the pump and cannula, can be neglected. In contrast, for an impaired inflow situation, the calculated pump flow based on pressure difference measurements can be misleading. Consequently, an improved pump management system is required to adjust the pump speed, the pump performance, to any kind of impaired inflow.

Background: The skeletonization technique of the internal thoracic artery (ITA) is used as a dissection technique for myocardial revascularization procedures. This study compared free flow between skeletonized ITA grafts and ITA pedicled grafts., Methods: The ITA pedicled grafts were sprayed and wrapped in sponges soaked in dilute papaverine solution in 14 patients and prepared with intraluminal papaverine injection in 18 patients. For 23 other patients, the ITA was skeletonized. We measured the first free flow from the distal ITA early after the start of cardiopulmonary bypass and the second free flow just before the ITA was grafted to the left anterior descending artery., Results: The first flow was greater in the skeletonized ITAs than in the ITA pedicled grafts with topical application of papaverine alone (38.9 +/- 15.8 versus 18.0 +/- 6.8 mL/min; p < 0.001). For the second flow, the pedicle grafts with intraluminal papaverine injection and the skeletonized ITAs showed greater flow rate than the pedicled grafts with topical application of papaverine (67.4 +/- 25.5 and 59.7 +/- 22.5 versus 38.1 +/- 13.1 mL/min; p < 0.005 and p < 0.05, respectively), but there was no significant difference between the former two groups (p = 0.53)., Conclusions: Skeletonization of the ITA is as efficient a strategy to increase the flow as intraluminal papaverine injection for the ITA pedicled graft. When the ITA is harvested in a skeletonized fashion, arterial spasm and reduced early flow can be avoided, even without intraluminal injection of papaverine.

To identify predictors of arterial graft patency, we followed up 30 internal thoracic arterial grafts and 23 right gastroepiploic arterial grafts in situ with patency documented during postoperative angiography. After 24 months of follow-up on average, repeat angiography detected that one internal thoracic artery and two gastroepiploic arteries were anatomically occluded and that the other three gastroepiploic arteries were nonfunctioning. The logistic regression model identified a relationship between graft patency and competitive flow, which was detected as stenosis in the recipient coronary arteries (coefficients, p < 0.05; model, Hosmer-Lemeshow chi2 statistic 3.59, p = 0.89). The linear regression model demonstrated that changes in graft luminal diameter correlated with competitive flow (p < 0.01), smoking history (p < 0.05), and type of arterial grafts (p < 0.001) (R2 = 0.40, adjusted R2 = 0.36). The findings suggest a temporal relationship between competitive flow and prognosis of arterial graft.

The internal thoracic artery (ITA) is the conduit of choice for coronary artery bypass grafting (CABG). This study, utilizing a canine model, evaluates cryopreserved ITA. Sixteen ITAs were harvested and cryopreserved according to United CryoInstitute protocol. Test conduits, 5 cm long and 4 mm mean diameter, were anastomosed to the ligated carotid artery of an unmatched mongrel recipient, above and below the site of native artery ligation. Graft patency was assessed by angiography at 14 days (early) and 980 days (late) postoperatively. Catheterization of the 16 vessels identified three (18%) early and one (6%) late graft occlusion. Ninety days postoperatively, each dog was killed and the graft harvested for histopathological and functional evaluation. Morphologic evaluation, using conventional staining, showed preserved cellular structure, decrease in smooth muscle cells and distorted endothelial layer. Immunocytochemistry, using an antibody against prostacyclin (PGI2), detected PGI2 immunoactivity in the ITA smooth muscle cells. An in vitro assay performed on the arterial rings confirmed preserved functional integrity of the vascular endothelium and smooth muscle. These findings suggest that cryopreserved ITA may have potential as a substitute graft, in devising conduit strategies for primary or reoperative coronary bypass surgery.

Purpose: The aim of this study was to show the parallel evolution of the pulsatility index of the uterine artery and the one of the median thoracic artery., Study Design: The study involved seven volunteer women, below 38, suffering from premature ovarian failure, who received E2 and progesterone replacement therapy. Plasma levels of E2, progesterone, follicle stimulating hormone and luteinizing hormone were measured and PI were studied and compared before treatment and on Days 13, 27 and 41., Results: Before treatment, a high-resistance vascular for both arteries is uniformly found. The curves show with the increasing of the E2 plasma levels, a decrease in the PI of UA and MTA with a fall at Day 13. We compared the mean values in MTA and UA PI. No statistical difference between the three mean values in PI obtained at Day -1, Day 13 and Day 41 was demonstrated., Conclusion: The results suggest that median thoracic artery is a target organ artery. Such as the UA, the MTA vascular resistance is according to the variations of plasma levels of E2. In consideration of it rectilinear and superficial type, this led us to study this artery when we use different sorts of replacement therapy, and particularly in the oocyte donation program.

The aim of this study was to compare changes in Doppler ultrasound studies of the fetal circulation in normal pregnancies with a group of pregnancies complicated by proteinuric pregnancy-induced hypertension (PPIH), delivery of a small-for-gestational-age (SGA) baby, or both. A total of 167 uncomplicated pregnancies with a term delivery of an appropriately grown baby (AGA) were used to define the normal range. Altogether, 123 high-risk pregnancies with a known outcome constituted the study group. A color duplex ultrasound machine was used to perform biometry and fetal Doppler studies. Measurements obtained from the fetal circulation included the umbilical artery (UA) pulsatility index (PI), the middle cerebral artery (MCA) PI and time-averaged velocity (TAV), the thoracic aorta (AO) PI and TAV. In addition, the ratio between the MCA PI and UA PI, the MCA PI and the AO PI, and the product of the MCA PI and AO TAV were used in the analysis. A total of 105 pregnancies had a complicated outcome. They were divided into three categories: PPIH only (pregnancies complicated by PPIH with the delivery of an AGA fetus, n = 17), SGA only (delivery of an SGA baby, with no evidence of PPIH, n = 55), and PPIH + SGA (pregnancies complicated by pre-eclampsia and delivery of an SGA baby, n = 37). The PPIH + SGA group represented true clinical intrauterine growth retardation. Cross-sectional reference ranges were created using the observations from the normal group. z-scores (standard deviation from the mean of the normal range) of the last observations made before delivery were calculated for each of the vessel velocimetry measurements and ratios. The statistical significance of z-score values was calculated using analysis of variance. The MCA and UA PI values showed the greatest deviation for any single-vessel parameter. The ratios of fetal Doppler indices (MCA/UA PI ratio, MCA/AO PI ratio and the MCA PI/AO TAV index) demonstrated greater deviation from normal than any individual vessel. The UA PI z-score for PPIH+SGA delivering < 34 weeks gestation (2.92) was significantly greater than the z-score for PPIH+SGA delivering > or = 34 weeks (1.20, p < 0.05). Fetal Doppler indices, in particular ratios that include measurements obtained from the cerebral circulation, help in the recognition of the small fetus that is growth-retarded. At term, evidence of fetal hemodynamic redistribution may exist in the presence of a normal umbilical artery PI. Fetal Doppler indices provide information that is not readily obtained from more conventional tests of fetal well-being.(ABSTRACT TRUNCATED AT 400 WORDS)

Recent evidence has suggested that competitive flow is an important factor in early graft failure. In this case report an internal thoracic artery graft was used to revascularize an acute coronary artery dissection after balloon angioplasty. Subsequent angiography 4 months later showed complete healing of the dissection, yet the internal thoracic artery graft remained widely patent in spite of the maximal competitive flow from the native coronary artery. This concurs with experimental results recently reported in The Annals regarding the physiologic adaptability of the internal thoracic artery graft to suit flow requirements and its versatility as the conduit of choice.

The dynamic reactivity and the acute, recruitable flow capacity of an internal thoracic artery (ITA) graft remains unclear. These experiments were conducted in 20 anesthetized dogs with the left ITA grafted to the circumflex artery, off pump, using a brief local occlusion. The left main coronary artery was occluded, rendering the entire left ventricle, including anterior descending artery and circumflex regions, totally dependent on the ITA graft. When the left main coronary artery was occluded, the ITA flow immediately increased more than fivefold (93.4 +/- 9.6 mL/min; mean +/- standard deviation), representing an absolute flow value three times higher than ITA flow measured in situ on the chest wall (27.5 +/- 9.6 mL/min; p < 0.05 versus control), and the ITA graft provided total resting flow requirements (93.4 +/- 9.6 mL/min) for both left anterior descending and circumflex coronary artery perfusion territories at levels comparable with measured native flow values (y = (0.9555)x + 21.9272; r = 0.976; p < 0.05). Pharmacologic challenge with adenosine (0.2 mg.kg-1.min-1 intravenously) significantly increased the graft flow (120.3 +/- 18.7 mL/min; p < 0.05 versus control), but also significantly decreased the mean arterial pressure (85.4 +/- 5.0 versus 74.6 +/- 6.1 mm Hg; p < 0.05). Phenylephrine (0.003 mg.kg-1.min-1 intravenously) significantly decreased ITA graft flow (81.2 +/- 9.0 mL/min; p < 0.05 versus control) despite significantly increased perfusion pressure (84.8 +/- 6.3 versus 108.2 +/- 8.6 mm Hg; p < 0.05 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

The flow reactivity of an internal thoracic artery (ITA) graft and a vein graft for multiple coronary beds in response to different modes of cardiac pacing remains unclear. These experiments were conducted in 14 anesthetized dogs with the ITA or the vein grafted to the circumflex coronary artery, off pump, using a brief local occlusion. The left main coronary artery was occluded, rendering the entire left ventricle totally dependent upon the ITA graft or the vein graft. When the left main coronary artery was occluded and the heart rate was 120 beats per min, graft flow was 93.4 +/- 9.6 ml per min in the ITA, and 96.1 +/- 10.4 ml per min in the vein graft. Atrial pacing to increase heart rates 25% to 150 beats per min increased both the ITA graft flow (110.3 +/- 9.7 ml per min, p < 0.05 versus flow in sinus rhythm) and the vein graft flow (109.8 +/- 7.9 ml per min, p < 0.05 versus flow in sinus rhythm). The increases in flow in both cases were not attributable to changes in perfusion pressure. In contrast, ventricular pacing to the same heart rate decreased systemic pressure slightly, but insignificantly. Despite the slight decrease in perfusion pressure, ventricular pacing increased ITA flow (107.9 +/- 8.4 ml per min, p < 0.05 versus flow in sinus rhythm), but the increase in vein graft flow was not significant compared with flow in sinus rhythm (102.1 +/- 7.3 ml per min, p = ns versus flow in sinus rhythm).(ABSTRACT TRUNCATED AT 250 WORDS)

In an effort to develop a noninvasive method to evaluate flow characteristics of the internal thoracic artery (ITA) graft after coronary artery bypass grafting, we performed color-flow duplex ultrasound studies of the right and left ITAs of 42 patients before and 5 weeks after bypass grafting. The ITA was visualized with a duplex scanner (5.0-MHz probe) through the first or second intercostal space. We recorded the diameter, peak systolic velocity, and end-diastolic velocity for each patient. Preoperative measurements of the native ITAs were obtained easily in all patients. Postoperatively, the unused right ITA was seen in all patients. Postoperative visualization of the left ITA graft was adequate to make reliable measurements in 40 patients (95%). Postoperative end-diastolic velocities of the unused right ITA and the left ITA graft were markedly higher than the preoperative end-diastolic velocities of the native ITAs (p < 0.001). Whereas there was a marked increase in the peak systolic velocity of the postoperative unused right ITA (p < 0.05), the postoperative peak systolic velocity of the left ITA graft was significantly lower than the preoperative value (p < 0.001). We conclude that postoperative visualization of the left ITA graft is possible with the use of color-flow duplex ultrasound. Ultrasonic surveillance of postoperative ITAs may reveal ITA graft velocity abnormalities before overt graft failure is manifested in the patient who has undergone coronary artery bypass grafting.

Isolated dog internal thoracic arteries (ITA) responded to norepinephrine and phenylephrine with concentration-related contractions, which were suppressed by prazosin, but not by yohimbine. Clonidine did not contract ITA. In coronary arterial strips, norepinephrine produced a relaxation. Isoproterenol relaxed coronary arterial strips contracted with serotonin but did not alter the tone of ITA. Forskolin and beraprost, an analog of prostaglandin I2, relaxed coronary and ITA strips to a similar extent. The beta-adrenoceptor density, assayed by [3H]dihydroalprenolol binding, was markedly less in ITA than in coronary arteries. Nicotine and transmural electrical stimulation did not alter the tension of ITA. Immunohistochemical study indicated that nerve fibers containing tyrosine hydroxylase immunoreactivity were markedly less in ITA than in coronary and mesenteric arteries. These results indicate that beta-adrenoceptor function and adrenergic innervation are considerably reduced in dog ITA. Norepinephrine-induced vasocontraction appears to be mediated by alpha 1-adrenoceptors in the arteries.

Transcutaneous duplex ultrasound can be used to image and quantify blood flow in the proximal part of the internal thoracic artery to coronary artery bypass grafts. In addition to providing information about graft patency and blood flow for follow-up purposes, the technique also provides an opportunity to study the physiology and pharmacology of the coronary circulation. In this paper we describe and attempt to interpret an unusual pattern of internal thoracic artery graft blood flow observed during inadvertent nitrate-induced syncope.

The authors have examined the possibility of usage of an internal thoracic artery (ITA) homograft as a new small caliber vascular substitute. Left subclavian artery to left atrial appendage shunts with fresh ITA homografts (n = 6) or ITA autografts (n = 5) were made by modified techniques of coronary artery bypass grafting in mongrel dogs (body weight, 11-16.5 kg). All recipient dogs had no anticoagulant therapy or immunosuppression. Inner diameter of the grafts was between 1.4 and 2.0 mm. Blood flow in ITA grafts was measured by electromagnetic flow meter. The graft flow was 6-14 ml/min before harvest and 67-220 ml/min just after implantation, and there was no significant difference between groups. Flow in the ITA homografts decreased significantly compared with ITA autografts 1 month after operation, but five of six ITA homografts were patent. Histopathology of the grafts showed vascular rejection in the homograft group. These results suggest that an ITA homograft with postoperative immunosuppression might be a new small caliber vascular substitute for coronary artery bypass grafting in ischemic heart disease and the systemic-pulmonary shunt operation in congenital heart diseases.

Ischemia of the donor airway remains a significant cause of morbidity after single-lung transplantation; serious manifestations may occur early (anastomotic dehiscence) or late (stricture). Direct, immediate revascularization of the donor bronchial arteries, using the recipient internal thoracic artery, was performed in 10 consecutive recipients of single-lung transplants for whom we procured the organs. Mean recipient age was 52.6 years (range, 43 to 59 years); 6 were male and 4 female. Recipient diagnoses were emphysema (6), obliterative bronchiolitis (2), pulmonary fibrosis (1), and primary pulmonary hypertension (1). Bronchial artery revascularization initially prolonged the ischemic time by only 15 to 20 minutes; this improved with experience. There was one early death and two late deaths in the series. Internal thoracic arteriography was performed 7 to 10 days postoperatively in all 9 surviving patients. There was excellent perfusion of the donor bronchial arteries in 7 of these 9 patients. Bronchoscopy was performed when clinically indicated. No patient had early or late airway healing complications at a median follow-up of 13 months (range, 6 to 16 months). We conclude that direct, immediate bronchial artery revascularization is feasible on a routine basis for single-lung transplantation, and airway healing has been excellent.

Purpose: Unexplained anatomic and physiologic factors account for the unacceptably high rate of paraplegia/paresis after thoracoabdominal aortic reconstruction. We assessed the neurologic significance of patent internal mammary arteries (IMAs) in a novel rat model of aortic clamping in which the aortic origins of the intercostal arteries (ICAs) were occluded., Methods: Twenty anesthetized, intubated, and halothane-ventilated adult male rats had catheters placed in the carotid and femoral arteries. ICAs arising from the aorta were divided at their origins through a left thoracotomy. IMAs were either divided (IMA-OUT, n = 10) or left intact (IMA-IN, n = 10). Proximal and distal descending aortic clamps were placed for 7 minutes. A neurologic deficit score (NDS) was assigned at 1, 4, 18, 24, and 48 hours by use of an established scoring system., Results: The mean IMA-IN NDS was statistically better than the mean IMA-OUT NDS at 1, 4, 18, and 24 hours with p = 0.0005, 0.0014, 0.0098, and 0.0151, respectively. Moreover, the mortality rate in the IMA-OUT group was statistically greater than in the IMA-IN group (p = 0.0036)., Conclusion: In this model, patent IMAs prevent paraplegia when the ICAs are occluded at their aortic origin and the aorta is clamped for 7 minutes.

With the advent of pressure breathing for +Gz (head-to-foot inertial loading) protection (PBG) and the development of improved extended coverage anti-G suits (ECGS) it has become important to expand our knowledge of the cardiopulmonary physiologic interrelationships of pressure breathing, anti-G suit protection, and the anti-G straining maneuver (AGSM). Although high levels of pressure breathing have been previously investigated, there was continuing concern within the aeromedical community regarding the introduction of COMBAT EDGE, a PBG system. Some of the concerns were: barotrauma, pneumothorax, air embolism, excessive transmural vascular pressures, possible cardiac valvular damage, and possible overdilation of the right ventricle from a surge in venous return following +Gz. This study describes the experimental preparation and results of a hemodynamic investigation to address some of these concerns using chronically instrumented miniature swine (MS).

In general, the right internal thoracic artery (ITA) is used less frequently as a graft than the left ITA in coronary artery bypass grafting. To determine whether there is an anatomic or hemodynamic rationale for the underuse of the right ITA, noninvasive measurements of right and left ITAs were performed in 171 patients before the bypass procedure. Transthoracic visualization of both vessels was accomplished using a color-flow duplex scanner (5.0-MHz probe) through the third intercostal space. The diameter (in millimeters), peak systolic velocity (in centimeters per second), and end-diastolic velocity (in centimeters per second) were measured in all but 2 patients. The mean right ITA diameter was 2.7 +/- 0.6 mm, the mean peak systolic velocity was 100 +/- 29 cm/s, and the mean end-diastolic velocity was 6 +/- 5 cm/s. Diameter and flow velocity measurements for the right and left ITA were similar in all patients (p = not significant). The measured values for both sites were independent of age and sex, or the presence of hypertension or diabetes mellitus (p = not significant). We conclude that no morphologic or physiologic differences exist between the right and left ITAs. The findings from this study indicate that color-flow duplex ultrasound imaging is a safe and reliable noninvasive technique in the preoperative assessment of the anatomic and functional characteristics of the right ITA before coronary artery bypass grafting.

The validity of alternative arterial conduits for myocardial revascularization in comparison to internal thoracic artery (ITA) has not been sufficiently defined. Evaluation of the functional in vivo vascular properties of the different conduits may be appropriate to give a perspective on long-term graft qualities. The intraoperative function of single free grafts to the left anterior descending artery (LAD) was compared in inferior epigastric (IEA, n = 13), internal thoracic (ITA, n = 12) and gastroepiploic artery (GEA, n = 12) conduits. Graft flows were measured at four points of time, 1) in situ free flow after distal dissection (IEA: 42.2 ml/min, ITA: 68.8 ml/min, GEA: 61.1 ml/min), 2) free flow following proximal grafting to the aorta (IEA: 48.1 ml/min, ITA: 63.7 ml/min, GEA: 84.2 ml/min), 3) selective graft flow after distal attachment to the LAD (IEA: 52.6 ml/min, ITA: 77.5 ml/min, GEA: 102.8 ml/min), and 4) selective LAD graft flow following paraverine (Pap) stimulation (IEA: 98.4 ml/min, ITA: 128.0 ml/min, GEA: 142.9 ml/min). Endothelium-dependent and -independent relaxation was evaluated by examination of the intraluminal graft pressures at mechanically controlled constant flow rates. Following stimulation with substance P (SP), the change of intraluminal pressure (dp) was similar in IEA (dp: -20.0 mmHg) and GEA grafts (dp: -21.1 mmHg). Only ITA conduits were less reactive to SP (-9.7 mmHg). The response to acetylcholine (ACh) could only be assessed in ITA (dp: -16.0 mmHg) and IEA (dp: -10.7 mmHg) grafts. Gastroepiploic arteries did not react on ACh stimulation (dp: +0.4 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

The rat pectoralis muscle can serve as a vascularized, innervated muscle flap model. The muscle, consisting of superficialis and profundus portions, is supplied by separate neurovascular systems. The vessels to pectoralis profundus (averaging 0.3 mm in diameter) can be taken in continuity with the axillary vessels (averaging 11 mm in diameter), which are used for transplantation. The profundus portion of muscle weighed an average of 1.8 g, and the average pedicle length was 0.9 cm. Nine of 11 transplanted muscles were viable, with intact circulation at 72 hours. An example of muscle transplantation for tissue defect coverage was attempted. The pectoralis profundus transplant was technically reliable, and the muscle bulk and contour could allow biochemical and functional studies.

The flow capacities of arterial and saphenous vein grafts in 100 patients who had coronary artery bypass grafting were compared under exercise conditions by continuous ventricular function monitoring, which records serial beat-to-beat radionuclide data and calculates left ventricular ejection fractions every 20 seconds. Ejection fraction profiles during graded bicycle exercise were divided into four types. In type A, the ejection fraction continued to increase. In type B, the ejection fraction initially increased, but decreased during the late exercise stage. In type C, the ejection fraction did not change. In type D, the ejection fraction continued to decrease throughout exercise. A decrease in ejection fraction, observed in type B or D, is an early indicator of myocardial ischemia. Before operation, 10 patients showed type A, 30 type B, 11 type C, and 49 type D responses. After operation, 68 patients showed type A, 21 type B, and 11 type C responses. Patients were divided into three groups according the type of bypass graft. Group 1 included 21 patients with two arterial grafts and vein grafts; group 2, 61 patients with an internal thoracic artery graft and vein grafts; group 3, 18 patients with only vein grafts. All of the grafts were patent on angiography. Eight patients (38%) in group 1 and 13 (21%) in group 2 showed a postoperative type B response, but none of the patients in group 3 had a postoperative type B response (p < 0.02). Seven of 8 patients in group 1 with postoperative type B responses had only arterial grafts to the left-side coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromogranin A (CGA) belongs to a family of highly acidic proteins which are co-stored and co-released with the catecholamines from the mammalian adrenal gland and occur in nmolar concentrations in the human circulation. A vascular function for the adrenomedullary released and circulating CGA has yet to be established. The present study reports on the novel vasoinhibitory effect of the N-terminal domain of the adrenomedullary CGA in isolated segments of the human internal thoracic artery (ITA) and saphenous vein (SV). The collective term vasostatin(s) refers to N-terminal fragments (CGA1-76 and CGA1-113) of apparent molecular weights 7 to 22 kD, to indicate their vascular inhibitory effects. The sustained contractions evoked by the potent vasoconstrictor peptide, endothelin-1 (ET-1) were suppressed when ITA and SV segments were preincubated for 15 min with vasostatins (72 nM). The vasoinhibitory effects were not dependent on an intact endothelium and suppression of the response to 35 nM ET-1 was approximately 77% and approximately 40% in endothelium-denuded ITA and SV segments, respectively. In endothelium-denuded SV segments the vasostatins suppressed the maximal sustained tension response but not the potency for ET-1, indicating that the vasostatin effect did not involve interference with ET-1 binding to its vascular receptor. Preincubation of endothelium-denuded SV segments with nifedipine (1 microM) inhibited the sustained response to ET-1 > or = 10 nM by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

The possible existence of arteriovenous anastomoses (AVAs) in skin regions of the head and thorax has been investigated using the synchronous vasomotion of the AVAs. Simultaneous pairs of blood velocity recordings were made using pulsed, bidirectional Doppler ultrasound. In each pair of registrations, blood velocity was recorded in a reference artery supplying a skin area known to contain AVAs (the radial artery) together with one of four other arteries investigated, i.e. the facial artery, the angular artery, the temporal artery, and the cutaneous branches of the lateral thoracic artery. The typical large, regular fluctuations in blood velocities caused by synchronous vasomotion in the AVAs in the skin of the hand and fingers were observed invariably in the radial artery. Similar flow variations were found in the angular artery. The fluctuations in this and the radial artery were, in turn, found to be synchronous. However, we have not been able to find the flow pattern characteristic of AVA vasomotion in the temporal artery or in the cutaneous branches of the lateral thoracic artery. These results show that the skin area of the nose supplied by the angular artery contains AVAs. These AVAs partly may explain the important role of face skin in temperature regulation. These results also support the earlier assumptions that there are no or very few AVAs in the skin areas supplied by the temporal artery and the cutaneous branches of the lateral thoracic artery.

Electromagnetic flowmetry and analogue computers were used to evaluate changes in great venous and arterial blood flow and resistance alterations in the vessels after nifedipine and verapamil in experiments with 12 anesthesized cats. The agents were demonstrated to increase cardiac output due to lower afterload and venous return, to redistribute cardiac output towards greater brain blood supply. The latter was caused by a more marked decrease in vascular resistance in the brachiocephalic arterial tree than in the descending thoracic artery. Blood flow changes in the great arteries determined those in the vena cava superior and inferior.

To determine whether previous sternotomy alters internal thoracic artery (ITA) anatomy and flow characteristics, a duplex scanner was used for noninvasive evaluation of the ITA in 59 patients who were scheduled for reoperative coronary artery bypass surgery. The left ITA was insonated through the third intercostal space by use of a duplex scanner (5.0 MHz probe). Measurements of the ITA diameter (mm) and peak systolic velocity (cm/sec) were obtained; ITA flow was calculated from velocity and cross-sectional area. These findings were compared with the values obtained from 105 patients who were scheduled to undergo first-time (primary) coronary artery surgery during the same time period. In the reoperative group, preoperative mean ITA diameter was 2.26 +/- 0.06 mm; this was not significantly different from the primary group's mean ITA diameter of 2.15 +/- 0.04 mm (p = 0.09). Mean peak systolic velocity was 79.9 +/- 2.4 cm/sec and calculated systolic blood flow was 204.6 +/- 13.1 ml/min in the reoperative patients, as compared with 83.3 +/- 2.1 cm/sec and 189.5 +/- 8.6 ml/min in the primary group, respectively. Values were similar in both groups for the peak systolic velocity (p = 0.31) and calculated systolic blood flow (p = 0.32). These results suggest that previous heart surgery or sternotomy does not adversely affect ITA anatomy and flow characteristics. We conclude that ultrasonic imaging is an easily applicable technique for preoperative assessment of ITA in patients who have undergone previous sternotomy.

Vascular effects of atrial natriuretic polypeptide (APII), i.e. the peptide hormone released from the atrial myocardium, were investigated in segments of the human internal thoracic artery (ITA) and saphenous vein (SV) with intact (+E) or injured (-E) endothelium. All segments were subject to several cycles of agonists in order to detect tachyphylactic or facilitatory responses. Opposite, indirect effects on the noradrenaline contracted ITA and SV were obtained in response to APII at a supranormal concentration (50 nM) which had no direct relaxing action on the isolated segments in vitro. In ITA the noradrenaline contractures in subsequent cycles were reduced to 41 +/- 21% (+E) and 28 +/- 9% (-E), but in SV they were enhanced to 211 +/- 115% (+E) and 483 +/- 242% (-E) of those before APII exposure. Thus under in vitro conditions ITA could be indirectly relaxed by APII via tachyphylactic effect on the noradrenaline contracture. SV, on the other hand, was markedly potentiated by APII in its noradrenaline response. In injured endothelium these opposite effects were aggravated.

The diastolic flow of the retrograde internal mammary artery (IMA) was calculated in 30 patients and compared with the expected coronary flow of the left ventricle and that of specific branches. Arterial pressure and free flow were measured in the proximal and distal IMA as well as in the superior epigastric and musculophrenic arteries. Systolic and mean arterial pressure were significantly higher in the proximal IMA than in any other site, but diastolic pressure was comparable. Overall and diastolic antegrade IMA flows (77 +/- 6 and 44 +/- 3 mL/min) were significantly greater than the retrograde flows through the distal IMA (18.5 +/- 2 and 11.5 +/- 1 mL/min), musculophrenic artery (13.3 +/- 1 and 7.9 +/- 1 mL/min), and superior epigastric artery (5.3 +/- 0.4 and 3.1 +/- 0.2 mL/min). Only patient-size-related variables correlated significantly with retrograde IMA flow. Diastolic retrograde IMA flow represented 8.5% +/- 0.6% of the expected left ventricle coronary flow and in 12 patients (40%) was greater than the expected flow of at least one posteroinferior coronary artery. Based on these data, the retrograde IMA may adequately perfuse the posterior descending or other posterolateral coronary branches in select patients. Previous measuring of the retrograde flow is mandatory.

The internal mammary artery has been advocated for use in coronary artery bypass grafting because of its excellent long-term patency. We compared the flow capacities of internal mammary artery and saphenous vein grafts under exercise conditions by means of radionuclide angiocardiography. Fifty-two patients were divided according to the type of bypass graft done to the left anterior descending artery: group 1 comprised 27 patients with the internal mammary artery graft, and group 2 included 25 patients with the saphenous vein graft. Saphenous vein grafts were placed into the right and circumflex systems. Before the operation, global and regional ejection fractions decreased similarly in both groups with exercise. After the operation, the global ejection fraction measured in groups 1 and 2 increased significantly from 54% +/- 2% to 57% +/- 2% and from 54% +/- 1% to 60% +/- 2%, respectively, the anteroseptal ejection fraction from 29% +/- 1% to 32% +/- 2% and from 29% +/- 1% to 35% +/- 1%, respectively, and the apical ejection fraction from 75% +/- 3% to 82% +/- 2% and from 77% +/- 2% to 86% +/- 2%, respectively. There were no differences in exercise-induced increases in the global and regional ejection fractions between groups 1 and 2. Six patients in group 1 had exercise-induced wall motion abnormalities at the anteroseptal and/or apical segments. In contrast, patients in group 2 had no exercise-induced wall motion abnormalities at these segments (p less than 0.05, group 1 versus group 2). Results of this study show that internal mammary artery grafts respond to the increased blood flow demand of exercise in essentially the same way as saphenous vein grafts. However, there seems to be a slightly greater potential for inadequate flow in patients with the internal mammary artery graft, as evidenced by the small group of patients with exercise-induced wall motion abnormalities.

When the rabbit thoracic artery was stimulated with submaximal concentrations of agonist [40 mM K+, 30 microM prostaglandin F2 alpha (PGF2 alpha) or 7 microM histamine], about 90% of a maximal contraction occurred. Each agonist induced a rapid development of contraction followed by a sustained response. The maximal rate of force generation stimulated with PGF2 alpha was twice that seen with K+ or histamine. Stimulation with 40 mM K+ increased the extent of monophosphorylated 20 kDa myosin light chain (MLC-P) for up to 1 min to a maximal value of 38.8 +/- 1.0%, there was a subsequent rapid decrease and the MLC-P level remained just above the basal value for 40 min (6.8 +/- 3.0%). In the case of stimulation with 7 microM histamine, MLC-P level increased rapidly and was sustained for up to 40 min (28.0 +/- 4.9%). In contrast to the stimulation with K+ or histamine, PGF2 alpha induced both mono- and diphosphorylated MLC20 (MLC-P and MLC-P2 respectively) at a low concentration (3 microM). The monophosphorylation of MLC20 induced by 30 microM PGF2 alpha reached the maximal value of 32.8 +/- 5.2%, and was sustained for up to 40 min (15.2 +/- 5.4%). The diphosphorylation of MLC20 increased rapidly (7.4 +/- 4.0% at 5 min), then decreased to the basal value within 40 min. These results suggest that different modes of stimulation of smooth muscle contraction produce different profiles of MLC20 phosphorylation. The implications of these observations are that the diphosphorylated form, specifically induced by certain agents, may modify the mode of contraction of the aortic artery.

Both the internal mammary artery and the saphenous vein are used to construct coronary-artery bypass grafts. We hypothesized that the release or production of endothelium-derived relaxing factor, which regulates blood flow and inhibits platelet function, may differ in venous and arterial grafts. We therefore studied endothelium-dependent relaxation in internal mammary arteries, internal mammary veins, and saphenous veins obtained from 58 patients undergoing coronary bypass surgery. Vascular rings with and without endothelium were suspended in organ chambers, and isometric tension was recorded. Acetylcholine (10(-8) to 10(-4) M), thrombin (1 U per milliliter), and adenosine diphosphate (10(-7) to 10(-4) M) evoked potent endothelium-dependent relaxation in the mammary artery but weak response in the saphenous vein (P less than 0.005; n = 6 to 27). In the mammary artery, relaxation was greatest in response to acetylcholine (86 +/- 4 percent reduction in norepinephrine-induced tension), followed by thrombin (44 +/- 7 percent) and adenosine diphosphate (39 +/- 8 percent). In the saphenous and mammary veins, relaxation was less than 25 percent. Relaxation was unaffected by indomethacin but was inhibited by methylene blue and hemoglobin (P less than 0.005 and 0.01, respectively), which suggests that endothelium-derived relaxing factor was the mediator. Endothelium-independent relaxation in response to sodium nitroprusside was similar in arteries and veins. We conclude that endothelium-dependent relaxation is greater in the mammary artery than in the saphenous vein. The possibility that this contributes to the higher patency rate among arterial grafts than among venous grafts will require further study.

The blood velocities in peripheral arteries were measured by pulsed Doppler ultrasound before, during and after electrotherapy treatment. 43 experiments with "Diadynamic", "High Voltage" and "Interference" treatment were performed on 22 healthy subjects aged 21-65 years. This treatment did not lead to an increase in mean blood velocities in the arteries supplying the area concerned. The intensities of stimulation were below the threshold for inducing muscle contractions. As discomfort due to the sensation of the electrical stimulation arose, a transitory decrease in velocities occurred. Simultaneous measurements from corresponding arteries on the treated and untreated sides showed no difference in blood velocity variation pattern. It is thus likely that the transient vasoconstrictor effect related to treatment is mediated by the sympathetic nervous system.

In previous studies longitudinal vibrations have been found to reduce active force development in smooth muscle, possibly due to a direct action on the contractile mechanism. In the present experiments the inhibitory effect of vibrations on isometric tension was studied in isolated preparations of the rat portal vein, the rabbit thoracic aorta and the anterior byssus retractor muscle (ABRM) of the Mytilus edulis. The results demonstrate that vibrations of appropriate frequency and amplitude caused prompt inhibition of contractile tension and that complete recovery of active force normally occurred after cessation of vibration in vertebrate smooth muscle as well as during the phasic contraction of ABRM. However, in the "catch" of the ABRM there was no regain in force following the vibration induced inhibition. The contractile proteins are considered to be a locked state during the catch situation. Thus, this contracted state seems to be released by vibrations. It is therefore concluded that vibrations do interfere with the interrelationship between the myofilaments. This conclusion supports the previously forwarded hypothesis that vibrations act by increasing the rate of detachment of actin-myosin crosslinks in vertebrate smooth muscle.

The function of beta-adrenoceptors in the human internal mammary artery was studied in vitro to predict the way in which the internal mammary artery graft would respond to beta-adrenergic agonists and antagonists given in the perioperative period. Ring segments of the distal internal mammary artery obtained from patients not receiving beta-blocker therapy were mounted in organ baths and isometric wall force was measured. For comparison, similar experiments were conducted on segments of canine coronary artery, a vessel known to have powerful beta-adrenoceptor function. All arteries were precontracted with potassium or the thromboxane mimetic agent, U46619, before isoproterenol cumulative concentration-relaxation curves were constructed. In the human internal mammary artery, the maximum relaxation induced by isoproterenol was only 14% of the potassium-induced contraction and 24% of the U46619-induced contraction. These responses were weak compared with 54% and 86% for beta-adrenoceptor relaxation measured in corresponding experiments in the canine coronary artery. In all experiments, propranolol antagonized the relaxation induced by isoproterenol. These studies suggested that the human internal mammary artery has only a small number of beta-adrenoceptors. We conclude that beta-adrenoceptors would contribute little to the reactivity of the human internal mammary artery graft to sympathomimetic drugs.

This study analyses the static and dynamic characteristics of the flow curves obtained by continuous wave Doppler flow velocity analysis in the internal mammary artery (IM) under normal conditions and after left anterior descending coronary artery by-pass. The IM flow velocity curve has the characteristics of a muscular artery both in basal conditions and during hyperventilation and Valsalva manoeuvre. On the other hand, the by-passed IM shows a typically phasic flow velocity curve, the diastolic flow prevailing over the systolic as is commonly the case in the coronary circulation. This curve also shows variations characteristic of the coronary circulation during Valsalva manoeuvre, whereas it is not affected by the alterations induced by hyperventilation in the area of the respiratory muscles. Continuous wave Doppler flow analysis of the by-passed IM can therefore be considered a reliable method for evaluating coronary flow in man. The fact that this method is non-invasive makes it obviously advantageous and widens its field of application not only to strictly diagnostic evaluations but also to physiopathological and therapeutical ones.

A large number of papers treat the tensile properties of arterial wall, but few treat compressive properties. Almost everybody assumes incompressibility; few have measured the vessel wall fluid extrusion due to compressive loading. In this work, uniaxial compressive force is applied directly on rabbit thoracic artery in the radial direction to study its constitutive equation under compressive stresses. The resulting stress-strain curves show that the wall material becomes increasingly stiffer at larger compressive strain, quite similar to the behavior in tension. A pseudo-strain energy function of the exponential type which has been applied successfully on the tension side is used to identify the material constants on the compression side. The material constants are identified in two ways: with and without the assumption of incompressibility. To determine the compressibility of the wall, the fluid extrusion accompanying this type of loading is measured, and is found to be in the range of 0.50-1.26% of the undeformed tissue volume per 10 kPa compressive stress loading in the radial direction. At compressive stresses higher than 30 kPa, the percentage of fluid extrusion per unit compressive stress decreases. At this degree of fluid extrusion the tissue is only slightly compressible (or nearly incompressible). However, the use of incompressibility assumption in the stress-strain relationship results in a set of material constants which is very different from that derived without that assumption.

Diagnostic imaging of the heart has, with the exception of echocardiography, employed techniques utilizing ionizing radiation. NMR imaging, a new technique, not only can generate images with spatial resolution closely approaching that of x-ray computed tomography without ionizing radiation, but can potentially detect the presence of intrinsic tissue damage. Although the exact role that NMR techniques will play in the assessment of cardiac disease is not currently defined, there are many instances where NMR may provide both unique and complementary information when compared with existing modalities.

The internal mammary artery has excellent long-term patency when used as a conduit for coronary artery bypass, and clinical and experimental studies have shown that blood flow through an internal mammary artery graft is satisfactory for most coronary artery branches. Multiple distal anastomoses from a single internal mammary artery, either with sequential anastomoses or with a Y-graft, might require additional blood flow through the vessel, and there has been concern that the flow capacity of the internal mammary artery is insufficient with these techniques. To better define the immediate postoperative flow capacity and pattern of the internal mammary artery, we performed experiments in seven dogs in which the left internal mammary artery was anastomosed to the circumflex coronary artery. In situ, blood flow in the internal mammary artery was 27 ml/min. Blood flow was 63 ml/min in the circumflex coronary artery and 42 ml/min in the left anterior descending coronary artery. After anastomosis of the left internal mammary artery to the circumflex coronary artery, the left main coronary artery was ligated; flow through the bypass graft increased to 92 ml/min, and systemic hemodynamics remained stable. Isoproterenol stimulation further increased flow through the left internal mammary artery graft to 160 ml/min. This study suggests that the canine internal mammary artery is capable of substantial early increase in flow and can, in fact, support the entire left coronary circulation.

The long-term patency of the internal mammary artery (IMA) graft is of considerable interest owing to its extensive use in myocardial revascularization. The aim of the present study was to elucidate the role of endothelium in modulating the responses of the porcine IMA to several vasoactive drugs. Isolated ring segments of porcine IMA contracted in a reproducible and dose dependent manner to phenylephrine, potassium chloride and the thromboxane mimic U46619, but the responses to serotonin, histamine and ATP were significantly less prominent. Both acetylcholine and bradykinin elicited endothelium-dependent relaxation which was not inhibited by indomethacin, but by methylene blue, an inhibitor of soluble guanylate cyclase. These two endothelium-dependent drugs and two endothelium-independent relaxing drugs, nitroprusside and nitroglycerin relaxed the IMA in a dose dependent manner which was associated with an elevation of cyclic GMP. The endothelium dependent vasodilator peptides such as bradykinin contain L-arginine in their sequence. Benzoyl derivatives of L-arginine but not L-arginine relaxed the IMA in a dose dependent manner. These data confirm and extend exploratory studies performed with a simpler vascular model which indicate that the precursor of endothelium derived relaxing factor (EDRF) is an arginine moiety.