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We aimed to study the physiological effects of diet supplemented with copper (Cu) nanoparticles (NPs). During the eight weeks of the experiment, young Wistar rats (at seven weeks of age, n = 9) were supplemented with 6.5 mg of Cu either as NPs or carbonate salt (Cu6.5). A diet that was not supplemented with Cu served as a negative control (Cu0). The impact of nano Cu supplementation on lipid (reflected as thiobarbituric acid reactive substances-TBARS) and protein peroxidation (thiol and carbonyl groups) in blood plasma as well as the influence on the vasodilatory mechanism(s) of isolated rat thoracic arteries were studied. Supplementation with Cu enhanced lipid peroxidation (TBARS) in NP6.5 (x2.4) and in Cu6.5 (x1.9) compared to the negative control. Significant increase in TBARS was also observed in NP6.5 (x1.3) compared to the Cu6.5 group. The level of thiol groups increased in NP6.5 (x1.6) compared to Cu6.5. Meanwhile, significant (x0.6) decrease was observed in the Cu6.5 group compared to the negative control. Another marker of protein oxidation, carbonyl groups increased in NP6.5 (x1.4) and Cu6.5 (x2.3) compared to the negative control. However significant difference (x0.6) was observed between NP6.5 and Cu6.5. Arteries from Cu supplemented rats exhibited an enhanced vasodilation to gasotransmitters: nitric oxide (NO) and carbon monoxide (CO). An enhanced vasodilation to NO was reflected in the increased response to acetylcholine (ACh) and calcium ionophore A23187. The observed responses to ACh and CO releasing molecule (CORM-2) were more pronounced in NP6.5. The activator of cGMP-dependent protein kinases (8-bromo-cGMP) induced similar vasodilation of thoracic arteries in NP6.5 and Cu0 groups, while an increased response was observed in the Cu6.5 group. Preincubation with the inducible nitric oxide (iNOS) synthase inhibitor- 1400W, decreased the ACh-induced vasodilation in NP6.5, exclusively. Meanwhile the eicosanoid metabolite of arachidonic acid (20-HETE) synthesis inhibitor-HET0016, enhanced vasodilation of arteries from Cu0 group. In conclusion, this study demonstrates that supplementation with nano Cu influences oxidative stress, which further has modified the vascular response., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Impaired endothelium-dependent relaxation (EDR) is a hallmark of endothelial dysfunction. A deficiency of tetrahydrobiopterin (BH 4 ) causes endothelial NOS to produce ROS rather than NO. PPARδ is an emerging target for pharmacological intervention of endothelial dysfunction. Thus, the present study examined the role of PPARδ in the regulation of dihydrofolate reductase (DHFR), a key enzyme in the BH 4 salvage pathway., Experimental Approach: Gene expression was measured by using qRT-PCR and western blotting. Biopterins and ROS were determined by using HPLC. NO was measured with fluorescent dye and electron paramagnetic resonance spectroscopy. Vasorelaxation was measured by Multi Myograph System., Key Results: The PPARδ agonist GW501516 increased DHFR and BH 4 levels in endothelial cells (ECs). The effect was blocked by PPARδ antagonist GSK0660. Chromatin immunoprecipitation identified PPAR-responsive elements within the 5'-flanking region of the human DHFR gene. The promoter activity was examined with luciferase assays using deletion reporters. Importantly, DHFR expression was suppressed by palmitic acid (PA, a saturated fatty acid) but increased by docosahexaenoic acid (DHA, a polyunsaturated fatty acid). GSK0660 prevented DHA-induced increased DHFR expression. Conversely, the suppressive effect of PA was mitigated by GW501516. In mouse aortae, GW501516 ameliorated the PA-impaired EDR. However, this vasoprotective effect was attenuated by DHFR siRNA or methotrexate. In EC-specific Ppard knockout mice, GW501516 failed to improve vasorelaxation., Conclusion and Implications: PPARδ prevented endothelial dysfunction by increasing DHFR and activating the BH 4 salvage pathway. These results provide a novel mechanism for the protective roles of PPARδ against vascular diseases., (© 2019 The British Pharmacological Society.)

In this study, we aimed at performing a histomorphometric analysis of human left internal thoracic artery (ITA) samples as well as at correlating the histomorphometric findings with the clinical profile, including risk factors and medication. Distal segments of ITA were obtained from 54 patients undergoing coronary artery bypass grafting. Histological observation was performed in paraffin-embedded transverse sections of ITA through four staining protocols: hematoxylin-eosin, van Gieson, Masson's trichrome and von Kossa. Morphometric analysis included the intimal width (IW), medial width (MW) and intima/media ratio (IMR). No overt atherosclerotic lesions were observed. Mild calcifications were observed across the vascular wall layers in almost all samples. Multivariable linear regression analysis showed associations between IW and IMR and the following clinical variables: age, gender, kidney function expressed as eGFR and myocardial infarction history. Age (odds ratio = 1.16, P = 0.004), female gender (odds ratio = 11.34, P = 0.011), eGFR (odds ratio = 1.03, P = 0.059) and myocardial infarction history (odds ratio = 4.81, P = 0.040) were identified as the main clinical predictors for intimal hyperplasia. Preatherosclerotic lesions in ITA samples from patients undergoing coronary revascularization were associated not only with classical cardiovascular risk factors such as age and gender, but also with other clinical variables, namely kidney function and myocardial infarction history., Competing Interests: The authors have declared that no competing interests exist.

The body plan of arthropods and vertebrates involves the formation of repetitive segments, which subsequently diversify to give rise to different body parts along the antero-posterior/rostro-caudal body axis. Anatomical variations between body segments are crucial for organ function and organismal fitness. Pioneering work in Drosophila has established that Hox transcription factors play key roles both in endowing initially identical segments with distinct identities and organogenesis. The focus of this review is on Alary Muscles (AMs) and the newly discovered Thoracic Alary-Related Muscles (TARMs). AMs and TARMs are thin muscles which together connect the circulatory system and different midgut regions to the exoskeleton, while intertwining with the respiratory tubular network. They were hypothesized to represent a new type of muscles with spring-like properties, maintaining internal organs in proper anatomical positions during larval locomotion. Both the morphology of TARMs relative to AMs, and morphogenesis of connected tissues is under Hox control, emphasizing the key role of Hox proteins in coordinating the anatomical development of the larva., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In systemic atherosclerosis develops the abnormal vascular tone which is associated with elevated calcium influx into smooth muscle cells and their calcification that may be proportional to the extent and severity of atherosclerotic disease. The goal of the present study was to investigate the responses of isolated human arterial samples to Ca²⁺-channel agonists and antagonists by varying the external Ca²⁺ concentration. Two dihydropyridine type calcium-channel blockers, amlodipine and cerebrocrast, were used in this study. The benzodiazepine-type calcium-channel blocker diltiazem, the benzimidazole derivative 1-acetyl-5,6-dimethoxy-2-methylthiobenzimidazole and 3,4'-bipyridine derivative milrinone were also used. Experiments were carried out on isolated human thoracic artery samples obtained from 74 patients, aged 38-88 years, during conventional myocardial revascularisation operations. The contraction of artery samples was recorded using an iFOT10 force transducer. Cumulative concentration-contraction curves of the tested agents (10⁻⁷ to 10⁻⁴ M) were established by varying the external Ca²⁺ concentration from 0.9 mM to 2.7 mM. Cerebrocrast, regardless of the Ca²⁺ concentration significantly increased arterial contraction, particularly at the lower Ca²⁺ (≈77%). Diltiazem, the benzimidazole derivative and milrinone caused the artery samples to relax at 10⁻⁴ M concentrations by 55%, 55% and 44%, respectively, when the external Ca²⁺ corresponded to the physiological standard. Shifting to lower or higher Ca²⁺ concentrations significantly altered the response of vessel samples by increasing their contraction. In conclusion, the present study shows that the response of isolated human thoracic artery samples to both the slow calcium channel suppressant diltiazem and to agonists of that channel (milrinone and the benzimidazole derivative) is regulated by the amount of calcium present in the physiological solution. Treatment with a slow calcium channel inhibitor, the 1,4-dihydropyridine derivative cerebrocrast, resulted in a response that was independent of the external Ca²⁺ concentration.

The mechanical behavior of blood vessels is known to be viscoelastic rather than elastic. The functional role of viscoelasticity, however, has remained largely unclear. The hypothesis of this study is that viscoelasticity reduces the stresses and strains in the vessel wall, which may have a significant impact on the fatigue life of the blood vessel wall. To verify the hypothesis, the pulsatile stress in rabbit thoracic artery at physiological loading condition was investigated with a quasi-linear viscoelastic model, where the normalized stress relaxation function is assumed to be isotropic, while the stress-strain relationship is anisotropic and nonlinear. The artery was subjected to the same boundary condition, and the mechanical equilibrium equation was solved for both the viscoelastic and an elastic (which has a constant relaxation function) model. Numerical results show that, compared with purely elastic response, the viscoelastic property of arteries reduces the magnitudes and temporal variations of circumferential stress and strain. The radial wall movement is also reduced due to viscoelasticity. These findings imply that viscoelasticity may be beneficial for the fatigue life of blood vessels, which undergo millions of cyclic mechanical loadings each year of life.

Ablation of the fibulin-5 gene (fbln5) in mice results in loose skin, emphysematous lungs and tortuous vessels. Additionally, fbln5(-/-) animals display an apparent increase in vascular sprouting from systemic and cutaneous vessels. From these observations, we hypothesized that a de-regulation of vascular sprouting occurs in the absence of endogenous fibulin-5. To test this hypothesis, vascular sprouts from the long thoracic artery were quantified and polyvinyl alcohol sponges were implanted subcutaneously in wild-type and fbln5(-/-) mice to assess fibrovascular invasion. Results showed a significant increase in in situ sprouting from vessels in fbln5(-/-) mice and a significant increase in vascular invasion, with no increase in fibroblast migration, into sponges removed from fbln5(-/-) mice compared with wild-type mice. Localization of fibulin-5 in wild-type mice showed the protein to be present subjacent to endothelial cells (ECs) in established vessels at the periphery of the sponge, and as a component of the newly formed, loose connective tissue within the sponge. These results suggest that fibulin-5 could function as an inhibitor molecule in initial sprouting and/or migration of ECs. To elucidate the molecular mechanism that drives the increased angiogenesis in the absence of fibulin-5, expression of vascular endothelial growth factor (VEGF) and the angiopoietins (Angs) was determined in sponges implanted for 12 days in wild-type and fbln5(-/-) mice. Quantitative RT-PCR showed message levels for VEGF and all three Angs to be elevated by several fold in the area of invasion of sponges from fbln5(-/-) mice compared with wild-type mice. Expression of Ang-1 was also shown to be elevated (30-fold) in vitro in aortic smooth muscle cells isolated from fbln5(-/-) mice when compared with wild-type cells, with no change in the expression of the Ang-1 mediating transcription factor, ESE-1. Taken together, these results suggest that the normal angiogenic process is enhanced in the absence of fibulin-5.

Here, we report the existence of endothelial precursor (EPC) and stem cells in a distinct zone of the vascular wall that are capable to differentiate into mature endothelial cells, hematopoietic and local immune cells, such as macrophages. This zone has been identified to be localized between smooth muscle and adventitial layer of human adult vascular wall. It predominantly contains CD34-positive (+) but CD31-negative (-) cells, which also express VEGFR2 and TIE2. Only few cells in this zone of the vascular wall are positive for CD45. In a ring assay using the fragments of human internal thoracic artery (HITA), we show here that the CD34+ cells of the HITA-wall form capillary sprouts ex vivo and are apparently recruited for capillary formation by tumor cells. New vessels formed by these vascular wall resident EPCs express markers for angiogenically activated endothelial cells, such as CEACAM1, and also for mature endothelial cells, such as VE-cadherin or occludin. Vascular wall areas containing EPCs are found in large and middle sized arteries and veins of all organs studied here. These data suggest the existence of a ;vasculogenic zone' in the wall of adult human blood vessels, which may serve as a source for progenitor cells for postnatal vasculogenesis, contributing to tumor vascularization and local immune response.

Objective: In patients with coronary artery disease, the concomitant presence of renal function impairment is associated with decreased survival. We aimed to assess whether in coronary artery diseased patients renal function impairment is associated with systemic vascular function, functional parameters of the renin-angiotensin system, or inflammation as potential mediators for cardiovascular risk., Methods and Results: We studied 125 patients, 87% male, with a mean age of 62.2+/-8.2 years; 72% had 3-vessel disease, and mean renal function was 74+/-13 mL/min per 1.73 m2. Internal thoracic artery rings were sampled during coronary bypass surgery and used for in vitro vascular measurements. We could not establish an association between endothelium-dependent vasorelaxation (response to methacholine) and renal function. In addition, vascular response to potassium chloride, phenylephrine, and angiotensin II were not associated with renal function. Finally, serum angiotensin-converting enzyme (ACE) activity, usage of ACE inhibitors, C-reactive protein, and soluble intercellular adhesion molecule 1 were not related to renal function., Conclusions: In coronary artery disease patients, mild renal function impairment is not associated with systemic vasomotor responsiveness, inflammation, or functional systemic parameters of the renin-angiotensin system. The relation between systemic endothelial dysfunction and mild renal insufficiency might be more complicated than previously thought.

Objective: Recent studies have shown that perivascular adipose tissue from the rat aorta secretes a substance that can dilate the aorta. The purpose of the present study was to examine whether this vasodilator is also present in human internal thoracic arteries., Methods: Vascular function of human internal thoracic arteries with and without perivascular adipose tissue was assessed with wire myography, and morphology was examined with light microscopy., Results: The presence of perivascular adipose tissue attenuated the maximal contraction to U 46619 and the contraction to phenylephrine (1 micromol/L) by 37% and 24%, respectively. Transfer of the solution incubated with a perivascular adipose tissue-intact vessel (donor) to a vessel without perivascular adipose tissue (recipient) induced a significant relaxation (36%) in the recipient artery precontracted with phenylephrine. Transfer of incubation solution with perivascular adipose tissue alone also induced a relaxation response in the recipient vessel (37%). The relaxation of the recipient artery induced by the transfer of incubation solution from the donor (artery with intact perivascular adipose tissue or perivascular adipose tissue alone) was absent in vessels precontracted by KCl (60 mmol/L) and was prevented by calcium-dependent potassium channel blockers (tetraethylammonium chloride, 1 mmol/L; iberiotoxin, 100 nmol/L), but not by the voltage-dependent potassium channel blocker 4-aminopyridine (1 mmol/L) and the adenosine triphosphate-dependent potassium channel blocker glibenclamide (10 micromol/L)., Conclusions: Perivascular adipose tissue in human internal thoracic arteries releases a transferable relaxation factor that acts through the activation of calcium-dependent potassium channels. Because perivascular adipose tissue is often removed in coronary artery bypass grafting, retaining perivascular adipose tissue might be helpful in reducing the occurrence of vasospasm of the graft vessels.

Background: Complex use of arterial conduits has resurrected concerns about the adequacy of conduit flow. The T-graft is the extreme example of this trend. Our purpose was to identify the limitation of single source inflow and to compare flow capacity with completion coronary flow., Methods: Between February 1999 and November 2001, 372 patients underwent total arterial revascularization with the T-graft alone. Intraoperative flows were recorded for each limb of the T-graft before and after distal anastomoses in 204 patients. Independent predictors of T-graft flow were identified by multivariate analysis., Results: Free flow for the radial arterial (RA) limb was 161 +/- 81 mL/min, the internal thoracic artery (ITA) limb 137 +/- 57 mL/min (combined 298 +/- 101 mL/min) versus simultaneous limb flow of 226 +/- 84 mL/min giving a flow restriction of 24% +/- 14%. Completion coronary flow was 88 +/- 49 mL/min for the RA, 60 +/- 45 mL/min for the ITA, and 140 +/- 70 mL/min for both limbs simultaneously to give a flow reserve (vs simultaneous free flow) of 160% or 1.6. Independent predictors of completion RA limb flow are RA proximal diameter (p = 0.005), number of anastomoses (p = 0.018), and target stenosis (p = 0.005)., Conclusions: A flow reserve of 1.6 compares favorably with an ITA flow reserve of 1.8 at 1-month postoperatively and 1.8 for both the ITA T-graft and the ITA/RA T-graft at 1-week postoperatively as reported by others. Proximal RA diameter and competitive coronary flow influence completion T-graft flow. These data quantitate the limitation of single source inflow of the T-graft configuration and support its continued use.

Background: This study was conceived to evaluate the effect of carbon dioxide insufflation on free internal thoracic artery flows., Methods: We studied 56 consecutive patients who underwent coronary artery bypass grafting in which the left internal thoracic artery was anastomosed to the left anterior descending artery. The first 26 consecutive internal thoracic arteries were harvested as a pedicled graft (group 1), and the next 30 consecutive internal thoracic arteries were dissected by using the carbon dioxide insufflation technique (group 2). The internal thoracic artery harvesting was performed by 2 experienced surgeons by using the same instrumentation and technique. First, free flows of the internal thoracic arteries were registered after distal cutting of the vessel in both groups. After the first measurements, diluted papaverine was sprayed on the internal thoracic artery pedicle only in group 1, and then second measurements were registered after 15 minutes in both groups. Hemodynamic parameters were recorded with each measurement., Results: The first free flow measurement was significantly higher in the carbon dioxide-insufflated internal thoracic arteries (group 2, 60 +/- 32 mL/min; group 1, 28 +/- 19 mL/min; P <.05). Although the second free flow measurement of the carbon dioxide-insufflated group was higher than in group 1, the difference was not statistically significant (68 +/- 46 mL/min vs 53 +/- 32 mL/min; P =.53)., Conclusions: Carbon dioxide insufflation of the internal thoracic artery is an efficient technique to increase the flow and seems to be safe, simple, and reliable. When the internal thoracic artery is harvested in a carbon dioxide-insufflated fashion, arterial spasm and reduced early flow may be avoided, even without vasodilator agents such as papaverine.

Objectives: To investigate the elastic properties of medium-size extracardiac arteries and veins between patients with and without left main stem coronary artery disease., Methods: The compliance, distensibility, and incremental elastic modulus (iEmod) of the internal thoracic arteries (n=53), long saphenous veins (n=38), and radial arteries (n=35) from 74 patients undergoing coronary surgery were studied in organ baths. Twenty-four patients had left main stem (LMS) disease and 50 non-LMS coronary disease., Results: Internal thoracic arteries from patients with LMS presented significantly lower compliance (-17%) and distensibility (-18%) and significantly higher iEmod (19%) than internal thoracic arteries from patients with non-LMS disease. Radial arteries from patients with LMS presented higher iEmod (50%) than radial arteries from patients with non-LMS disease. Furthermore, long saphenous veins from patients with LMS had reduced compliance (-45%), reduced distensibility (-40%) and increased iEmod (34%) compared to those from patients with non-LMS disease., Conclusions: LMS coronary disease is associated with a significantly reduced elasticity of extracardiac arteries and veins compared to non-LMS coronary disease. This finding suggests that widespread vascular elasticity defects may play a role in the development of LMS disease and be responsible for the higher incidence of early and late cardiovascular morbidity observed in this condition.

Background: Use of arterial grafts in coronary surgery is based on the excellent patency of the left internal thoracic artery (LITA) and an expectation that other arterial grafts-right internal thoracic artery (RITA) and radial artery (RA)-will give similar patencies, superior to saphenous vein. We examined patencies of arterial grafts in a practice with extensive use for more than 15 years., Methods: Consecutive postoperative angiograms of 2,127 arterial/coronary conduits were evaluated. Angiograms were performed for cardiac symptoms. Assessment was by two observers. String signs were considered as occlusions., Results: There were 2127 arterial conduits. Overall patencies were as follows: LITA, 96.4% (1296 of 1345); RITA, 88.3% (534 of 605); aortocoronary RA, 89.3% (158 of 177). The LITA patency to the left anterior descending artery was 97.1% (1131 of 1165); to the obtuse marginal artery it was 91.7% (165 of 180; p 0.01). The RITA pedicled graft patency was 86% (275 of 321) compared with free RITA, 91% (259 of 284; p = not significant). For RITA there was a hierarchy of patency for coronary territory grafted (left anterior descending artery best, right coronary/posterior descending artery worst) and for degree of coronary stenosis: if stenosis was less than 60%, patency was 65% (47 of 72); if stenosis was more than 60%, patency was 90.9% (485 of 533; p = 0.0001). Similarly for the radial artery there was higher patency with greater coronary stenosis. The LITA patency at 5 years was 98%, at 10 years it was 95%, and at 15 years it was 88%. The RITA patency at 5 years was 96%, at 10 years it was 81%, and at 15 years it was 65%. The radial artery patency at 1 year was 96% and at 4 years it was 89%. For 3,714 vein grafts also studied overall patency was 61% (2266 of 3214) with patencies of 95% at 5 years, 71% at 10 years, and 32% at 15 years., Conclusions: Excellent long-term patencies of arterial grafts are noted, superior to those of vein grafts. Patencies were influenced by conduit, by distribution, and by coronary artery stenosis.

Objective: We investigated the mechanism of the protamine action and the effects of free hemoglobin on protamine-induced responses in endothelium-denuded and-intact human internal thoracic artery (ITA) rings precontracted with phenylephrine (PE) or high KCl., Methods: Samples of redundant ITA obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system., Results: Acetylcholine (Ach, 10(-8)-10(-5) M) caused a concentration-dependent relaxation of PE-precontracted ITA rings. Free hemoglobin (0.1 and 0.5 microM) produced a concentration-dependent and significant decrease in sensitivity (pD(2)) and maximal contractility (E(max)) in response to Ach in PE-precontracted ITA rings (P<0.0001). Protamine (50-800 microg/ml), free hemoglobin (0.1 and 0.5 microM), nitric oxide (NO) blocker N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) or soluble guanylate cyclase inhibitor methylene blue (10 microM) administration did not cause a significant alteration on basal tonus of endothelium-intact or -denuded ITA rings. Protamine (50-800 microg/ml) induced concentration-dependent relaxation responses in ITA rings precontracted by either PE or high KCl. There was no difference in sensitivity or maximal response to protamine between the endothelium-intact and -denuded rings. Incubation of endothelium-intact or -denuded ITA rings with L-NAME or free hemoglobin or methylene blue did not cause a significant inhibition on relaxation responses to protamine. ITA ring contractions induced by stepwise addition of calcium to high KCl solution with no calcium were almost completely inhibited by protamine (P<0.0001)., Conclusions: It was suggested that protamine induced relaxation responses in human ITA rings is not NO- or endothelium-dependent but seems to depend on the interactions of protamine with calcium influxes and/or calcium release from intracellular stores in this tissue.

Objective: Internal thoracic artery (ITA) flow competition is a diversion of graft flow through intact ITA branches with a net decrease in perfusion to the grafted coronary. Although a widely acknowledged phenomenon, the conditions under which flow competition occurs have not been established. This is examined in a canine H-graft model., Methods: Eight dogs had a right ITA segment interposed (H-graft) between their in situ left ITA (LITA) and the snared left anterior descending (LAD) coronary artery. Proximal LITA and H-graft flows were measured at baseline and during pacing-induced tachycardia, phenylephrine-induced hypertension, and nitroprusside-induced hypotension. Flows were measured with the distal LITA open and occluded. Two additional animals were subjected to eight separate 2-min periods of LAD ischemia, after which post-ischemic H-graft flow measurements were obtained with and without distal LIMA occlusion., Results: During baseline conditions, proximal LITA flow was greater when the distal LITA was open rather than occluded (46+/-15 versus 35+/-12 ml/min, respectively; P=0.002), but H-graft flow did not change significantly (32+/-18 versus 35+/-18 ml/min, respectively; P=0.21). Similarly, occlusion of the distal LITA had no impact on H-graft flow during tachycardia, hypertension, or hypotension. Only in animals subjected to transient LAD ischemia did H-graft flow increase with distal LITA occlusion, albeit marginally (65+/-7-70+/-9 ml/min, occluded versus open, respectively; P=0.04)., Conclusions: Mild diversion of flow from the LAD was demonstrated during immediate post-ischemic coronary reperfusion only, and could not be elicited under any other physiologic condition. These data suggest that flow competition is unlikely to constitute a clinically significant limitation to the use of H-grafts or other modalities that leave ITA branches patent.

Background: Statins may enhance vascular function independently of effects on cholesterol. This study investigated the ability of statins to modulate the vascular recovery of arteries used as coronary bypass grafts., Methods: Specimens of radial artery and left internal thoracic artery were obtained during coronary artery bypass grafting. The specimens were divided into vascular rings, which were incubated in the absence or presence of cerivastatin (10(-6) mol/L) for either 2 or 24 hours. Using an organ bath technique, endothelial function was examined using acetylcholine (10(-9) to 10(-5) mol/L) after contraction by 3x10(-8) mol/L of endothelin-1., Results: Time-related endothelial dysfunction was shown in the control group of radial artery but not in the cerivastatin group: maximal endothelium-dependent vasodilation in the control and cerivastatin groups were 56.8% +/- 10.2% and 65.9% +/- 10.1% at 2 hours and 39.4% +/- 4.7% and 68.4% +/- 5.0% (p < 0.01, vs control) at 24 hours, respectively. On the other hand, in the left internal thoracic artery, those in the control and cerivastatin groups were 38.3% +/- 8.2% and 45.0% +/- 5.5% at 2 hours and 38.1% +/- 8.2% and 56.5% +/- 8.8% at 24 hours, respectively (NS)., Conclusions: In radial artery, cerivastatin significantly preserved endothelium-dependent vasodilation, which diminished with time in the control group. This could have very important implications in the clinical practice of coronary artery bypass grafting.

Background: A reduction in compliance of the large-sized cardiothoracic (central) arteries is an independent risk factor for the development of cardiovascular disease with advancing age., Methods and Results: We determined the role of habitual exercise on the age-related decrease in central arterial compliance by using both cross-sectional and interventional approaches. First, we studied 151 healthy men aged 18 to 77 years: 54 were sedentary, 45 were recreationally active, and 53 were endurance exercise-trained. Central arterial compliance (simultaneous B-mode ultrasound and arterial applanation tonometry on the common carotid artery) was lower (P:<0.05) in middle-aged and older men than in young men in all 3 groups. There were no significant differences between sedentary and recreationally active men at any age. However, arterial compliance in the endurance-trained middle-aged and older men was 20% to 35% higher than in the 2 less active groups (P:<0.01). As such, age-related differences in central arterial compliance were smaller in the endurance-trained men than in the sedentary and recreationally active men. Second, we studied 20 middle-aged and older (53+/-2 years) sedentary healthy men before and after a 3-month aerobic exercise intervention (primarily walking). Regular exercise increased central arterial compliance (P:<0.01) to levels similar to those of the middle-aged and older endurance-trained men. These effects were independent of changes in body mass, adiposity, arterial blood pressure, or maximal oxygen consumption., Conclusions: Regular aerobic-endurance exercise attenuates age-related reductions in central arterial compliance and restores levels in previously sedentary healthy middle-aged and older men. This may be one mechanism by which habitual exercise lowers the risk of cardiovascular disease in this population.

Vasodilation that occurs during normal pregnancy is associated with enhanced relaxation and decreased contractile response to agonists, which are in part due to increased stimulated and basal nitric oxide (NO). In preeclampsia and/or pregnancies carried at high altitude (HA), this normal vascular adjustment is reversed or diminished. We previously reported that HA exposure did not inhibit the pregnancy-associated decrease in contractile response to agonist or basal NO in guinea pig uterine arteries (UA). We therefore sought to determine whether altitude interfered with effects of pregnancy on endothelium-dependent relaxation through a reduction in stimulated NO. We examined the relaxation response to ACh in UA and bradykinin in thoracic arteries (TA) and effects of NO inhibition with 200 microM N(G)-nitro-L-arginine (L-NNA) in arterial rings isolated from nonpregnant and pregnant guinea pigs exposed throughout gestation to low altitude (LA, 1,600 m, n = 26) or HA (3,962 m, n = 22). In pregnant UA, relaxation to ACh was enhanced (P < 0.05) at both altitudes and NO inhibition diminished, but did not reverse, ACh relaxation. The effect of L-NNA on the relaxation response to ACh was less in HA than in LA animals (P = 0.0021). In nonpregnant UA, relaxation to ACh was similar in LA and HA animals. L-NNA reversed the relaxation response to ACh at HA but not at LA. In TA, relaxation to bradykinin was unaltered by pregnancy or altitude and was completely reversed by NO inhibition. These data suggest that effects of NO inhibition are diminished in UA during pregnancy at HA. Additional studies are needed to confirm whether these effects are mediated through inhibition of stimulated NO. HA exposure did not inhibit relaxation to ACh, perhaps because of stimulation of other vasodilators.

Objective: Total arterial myocardial revascularization may be achieved by using the 'Y-graft' techniques with different free arterial conduits anastomosed off the side of an in situ internal thoracic artery to reach distal coronary segments. This study was assessed to measure intraoperative graft flow, resistance and clinical outcomes., Methods: Seventy-six patients who underwent coronary artery bypass grafting during a time period of 27 months were enrolled in this prospective study. All patients received sequential grafting by using both internal thoracic arteries, inferior epigastric and right gastroepiploic artery joined as a composite Y graft. Intraoperative graft flow, resistance and derived variables were measured., Results: All patients except one showed good flow (ml/min and waveform) in either branch of composite graft. In one case, a low-flow situation through the graft was registered requiring surgical correction. Temporary occlusion of either branch did not significantly affect flow in the other side of the arterial Y. Mid-term follow-up (3 and 15 months) and angiographic studies showed a high graft patency rate., Conclusion: Composite arterial grafts provide excellent early and mid-term clinical results. Flow reserve of the left internal thoracic artery did not affect blood flow and resistance on either branch of the Y graft when temporary occlusion on the other side of the arterial Y was performed.

Objective: The internal thoracic artery (ITA) is the ideal conduit for coronary artery bypass grafting (CABG). The skeletonization technique of this arterial conduit has been proposed to reduce chest wall trauma, increase graft length and facilitate construction of sequential anastomoses. Nevertheless, some surgeons decline this technique because of potentially increased trauma to the ITA with impairment of flow. In this investigation we compared the free flow of skeletonized with that of pedicled ITA grafts., Methods: Two surgeons operated on 80 consecutive patients with coronary artery disease for elective CABG. In group I (n = 40), the left ITA was dissected using the skeletonization technique. In group II (n = 40), it was harvested as a pedicled graft. In 23 patients of group I both ITA's were dissected in skeletonized fashion for complete arterial revascularization. Diluted papaverine was instilled into the lumen of the ITA after distal transection of the vessel in both groups. Free flow of the ITA was registered before and 15 min after intraluminal application of diluted papaverine. Mean arterial pressure was maintained at 70 mmHg., Results: Before the application of papaverine, free flow of skeletonized and pedicled ITA grafts was identical between the two groups. After treatment with papaverine maximum free flow was significantly higher in the skeletonized ITA's (group I 197.2 (+/-66.6) ml/min; group II 147.1 (+/-70.5) ml/min; P < 0.05). There was no significant difference between free flow after dilatation of the left and right ITA in group I (left 197.2 (+/-66.6) ml/min; right 198.9 (+/-61.8) ml/min)., Conclusions: Preparation of the ITA with the skeletonization technique results in significantly, higher free flow capacity than in pedicled grafts. This may increase the safety of arterial revascularization by reducing the risk of ITA hypoperfusion syndrome.

Background: Intraoperative ultrasonography has the potential to provide anatomic and functional information about internal thoracic artery (ITA) graft, but this potential has been hindered by the relatively large standard probe. In this study, we used a color Doppler microprobe to evaluate ITA grafts., Methods: The subjects were 15 consecutive patients who underwent elective coronary artery bypass grafting either with cardiopulmonary bypass (n = 14) or without (n = 1). All patients underwent anastomosis of the left ITA to the left anterior descending artery. The ITA graft was assessed before the chest was closed, with the microprobe placed directly on the graft., Results: A good-quality color Doppler image of the ITA graft was easily obtained in all 15 patients within a few minutes. The ITA graft function was assessed by analyzing the shape of the pulsed Doppler wave. All ITA grafts were patent, and the mean graft diameter was 1.8 +/- 0.04 mm. The peak systolic velocity, peak diastolic velocity, and mean velocity were 52.0 +/- 14.9 cm/s, 58.3 +/- 22.4 cm/s, and 36.5 +/- 10.9 cm/s, respectively. The ratio of peak diastolic velocity to peak systolic velocity was 1.24 +/- 0.66. The ITA graft seemed to function well when the biphasic diastolic predominant flow appeared. The mean blood flow was 55.1 +/- 22.0 mL/min., Conclusions: Intraoperative ultrasonography using the microprobe provides adequate anatomic and hemodynamic information regarding ITA grafts. As the Doppler flow evaluation has high sensitivity and specificity, we suggest that intraoperative ultrasonography is useful for the assessment of these grafts.

Unlabelled: Surgeons have traditionally relied on ring preparations to predict how arterial bypass conduits will behave in the postoperative circulation., Objective: This study compared pharmacologic [norepinephrine (NE) challenge] and physiologic [arterial preload] responses of gastroepiploic (GEA) and internal thoracic (ITA) arteries in a standard static ring preparation and a dynamic perfusion system., Methods: Six GEAs (1.0-1.5 mm dia.) and six ITAs (1.5-2.0 mm dia.) 11 cm long were harvested from adult pigs and mounted on a computer controlled perfusion system. Inflow pressure was set at 80 mmHg and outflow resistance was adjusted to simulate high (80-90 ml/min) and low (15-20 ml/min) flow demands. NE response (10(-9)-10(-5) M) was measured under low flow conditions and at high flow conditions when distal arterial pressure (load) was reduced. NE response (10(-9)-10(-5) M) was also evaluated in arterial rings (ITA N = 6, GEA N = 6) with tensions adjusted to simulate the loads occurring at low flow (80 mmHg) and high flow (60 mmHg) situations., Results: In the static ring preparation, NE response [ED50] was similar for both GEA and ITA and was not affected by load. The dynamic preparation demonstrated that the GEAs were significantly more responsive to NE than the ITAs [ED50 high flow ITA 6.1 +/- 0.3**, GEA 7.2 +/- 0.3***; *P < 0.05 versus baseline, **P < 0.05 versus low flow values, ***P < 0.05 versus ITA]. Furthermore, in the dynamic preparation, NE response was profoundly affected by reduced load which occurs under high flow conditions [7.18 +/- 0.3 versus 6.1 +/- 0.3 under high flow and 5.8 +/- 0.1 versus no response under low flow conditions]., Conclusion: Static ring preparations do not discern differences between ITA and GEA susceptibility to spasm and fail to detect the effect of load. The dynamic preparation demonstrated significant differences between the GEA and ITA potential to spasm which is consistent with widespread clinical experience. Furthermore a dynamic preparation is highly sensitive to reduced load which occurs under high flow conditions. Although it is more demanding, the dynamic preparation provides superior information to the surgeon in predicting the behavior of arterial bypass grafts.

Objective: Competitive flow from patent native coronary vessels is implicated in the failure of internal thoracic artery (ITA) grafts, but it is not thought to affect saphenous vein graft (SVG) patency. This study examines instantaneous pressure and flow dynamics in left ITA and SVG grafts in competition with a patent left anterior descending (LAD) artery., Methods: SVG (3.0-4.0 mm) and ITA (1.5-2.0 mm) to proximal LAD (2.5-3.0 mm) coronary bypass was performed in 10 mongrel dogs. Flow and pressure were measured in the occluded (No Competition) and opened (Competition) ITA, SVG and LAD., Results: The ITA and SVG, when each was the sole inflow to the LAD, provided similar flow as the native LAD. During competitive flow, total LAD flow was preserved and flow in the ITA and SVG were reduced (8.20 +/- 1.25 and 10.00 +/- 1.73 ml/min; P < 0.005). SVG diastolic flow was reduced to 11.52 +/- 2.17 ml min (55.5%); P < 0.003. Flow in the SVG remained predominantly antegrade. In contrast, ITA diastolic flow was reduced more drastically, to 5.37 +/- 1.25 ml/min (80.7%); P < 0.0001. When the ITA was the only inflow to the LAD, there was delay in the LAD pressure wave. This delay disappears during competition due to the large, systolic retrograde flow up the ITA., Conclusion: The ITA, compared to the SVG, is a longer and narrower conduit with lower levels of flow during competition. Due to a delay in the pressure wave, the ITA flow is retrograde during early systole. Low levels of flow, with a markedly decreased diastolic phase, and the oscillating pattern in systole (retrograde/antegrade) may be poorly tolerated by the ITA endothelium and lead to graft deterioration.

Background: This study examines whether the measurement of internal thoracic artery (ITA) graft flow can determine the adequacy of the ITA-left anterior descending coronary artery (LAD) anastomosis., Methods: To study a wide range of clinical problems, we used a computer simulation of the cardiovascular system. The model included a time-varying elastance model of the heart, a systemic circulation represented by a multielement nonlinear model of the aorta and its major branches, a nonlinear model of the LAD circulation, and a model of the ITA bypass graft., Results: With a mild LAD stenosis, ITA graft flow was low and flow reversal occurred. As the percent stenosis increased, ITA flow and the percentage of ITA-to-total LAD flow increased. The ITA graft helped to maintain resting LAD blood flow. A partial obstruction (40%) at the ITA-LAD anastomosis reduced ITA graft flow at similar levels of LAD stenosis. However, overlap in flow values comparing a normal with a partially obstructed anastomosis occurred., Conclusions: Flow patterns in the ITA are highly dependent on the degree of stenosis of the LAD as well as the integrity of the anastomosis. The predictive power of ITA flow measurement increases with severe stenosis or total occlusion of the proximal LAD and with high coronary blood flow demands.

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.

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.

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.

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)

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.

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.

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 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)

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.

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.