Biochemical composition of human internal mammary artery and saphenous vein

The long-term patency of the internal mammary artery graft is better than that of the saphenous vein graft in coronary bypass surgery because of a low incidence of atherosclerosis in the internal mammary artery. In search of a possible biochemical explanation of the low degree of atherosclerosis in the internal mammary artery we compared the chemical compositions of human internal mammary artery and saphenous vein obtained from 37 patients undergoing coronary bypass surgery. The levels of esterified cholesterol and free cholesterol were higher in the internal mammary artery than in the saphenous vein (p less than 0.001 and p less than 0.01, respectively), but lower than the levels reported in previous studies for coronary arteries. The amount of collagen was higher in the saphenous vein (p less than 0.001). Heparan sulfate was the major glycosaminoglycan fraction in the internal mammary artery, probably reflecting the higher cellularity and thicker media in the arterial rather than in the venous tissue. The level of dermatan sulfate was higher (p less than 0.001) in the saphenous vein than in the internal mammary artery. This difference is in a direction that could favor atherogenesis in the saphenous vein graft.     

Human internal mammary artery produces more prostacyclin than saphenous vein

The patency rate of internal mammary artery grafts is reported to be better than that of saphenous vein grafts in myocardial revascularization operations. To identify a possible biochemical explanation for this phenomenon, we studied the production of prostacyclin by the internal mammary artery and saphenous vein in 11 patients. Segments of internal mammary artery and saphenous vein from each patient were incubated in Krebs-Henseleit buffer at 37 degrees C. After 15 minutes, the basal production of 6-keto-prostaglandin F1 alpha (prostacyclin metabolite) by the internal mammary artery was 152 +/- 39 pg/mg wet weight (mean +/- standard error of the mean), whereas the saphenous vein produced only 68 +/- 17 pg/mg (p less than 0.001). After 30 minutes, the internal mammary artery produced 179 +/- 42 pg/mg, whereas the saphenous vein produced 75 +/- 18 pg/mg (p less than 0.001). After the basal incubation period, the vessels were incubated with arachidonic acid (prostaglandin substrate) for 15 minutes. The internal mammary artery produced 49.4 +/- 9.9 pg/mg, whereas the saphenous vein produced only 22.6 +/- 9.8 pg/mg (p less than 0.01). These observations suggest that the capacity of the internal mammary artery to produce prostacyclin in both a basal and a stimulated state is greater than that of the saphenous vein. Since prostacyclin is a potent vasodilator and inhibitor of platelet function, these results provide a possible biochemical explanation for the clinically observed better patency rate of internal mammary artery grafts.     

Long-term fate of the internal mammary artery and saphenous vein grafts

Thirty-four patients, each receiving internal mammary artery (IMAG) as well as saphenous vein grafts (SVGs), returned with symptoms 3 to 12 years after operation and underwent angiographic studies. At a mean follow-up period of 6.8 years, two (6%) IMAGs were occluded and 33 (94%) were in excellent condition. Of the 57 SVGs, 28 (48%) were totally occluded, 12 (22%) had severe atherosclerosis, and only 17 (30%) were in good condition. Seven patients (20%) had new significant lesions in the ungrafted coronary arteries. Failure of SVGs was the predominant cause of symptoms in this group of patients. Late failure of the SVGs appears to be due to progressive atherosclerosis in the grafts. The IMAGs tend to remain free from atherosclerosis and perform much better than the SVGs in the long run.     

Lung function after coronary artery surgery using the internal mammary artery and the saphenous vein.

Lung volumes and arterial blood gas tensions in patients undergoing coronary artery surgery were compared in 77 patients given an internal mammary artery graft (group 1) and 33 patients given a saphenous vein graft only (group 2). Patients in both groups developed a severe restrictive ventilatory defect after surgery, more pronounced in those receiving an internal mammary artery graft. Mean (SEM) vital capacity in groups 1 and 2 was reduced to 36% (1.2%) and 45% (2.0%) of preoperative values on the second postoperative day (1.56 and 1.85 1 respectively), with some recovery by day 4 to 56% (1.2%) and 63% (2.1%) of preoperative values. The mean (SEM) arterial oxygen tension was 7.34 (0.13) kPa for group 1 and 7.46 (0.20) kPa for group 2 on day 2, rising to 8.39 (0.13) and 9.01 (0.23) kPa on day 4. Analgesic requirements were greater in the group receiving an internal mammary artery graft. Possible explanations for the differences between the effects of the two grafts include the higher frequency of pleurotomy, the placing of pleural drains, and additional surgical trauma when internal mammary artery grafts are used.     

Surgical treatment of unstable angina by saphenous vein and internal mammary artery bypass grafting.

During a 3 year period, direct myocardial revascularization was performed on an urgent basis in 48 patients with intermittent resting chest pain which persisted more than 24 hours despite in-hospital medical therapy and was accompanied by electrocardiographic changes representative of ischemia. Sixteen patients had saphenous vein (SV) grafts exclusively, and 32 patients each had one or two internal mammary artery (IMA) grafts with or without additional vein grafts. Follow-up ranges from 5 to 41 months (mean, 22 months). Twelve patients had single grafts to the left anterior descending coronary artery (LAD), 18 had double grafts, 16 had triple grafts, and 2 had quadruple grafts. The LAD required grafting in every patient. There was one operative death (2 per cent) and one late death from noncardiac causes. There were two (4 per cent) early postoperative myocardial infarcts and no late infarcts. Actuarial analysis projects a survival rate of 96 per cent 3 years postoperatively. Eighty-one per cent of the survivors are in Functional Class I, 17 per cent are in Class II, and 2 per cent are in Class III. All patients had postoperative angiography 2 weeks after operation. Eighty-six per cent of the SV grafts and all IMA grafts were open. No significant differences were observed between mean preoperative and postoperative left ventricular end-diastolic pressures or ejection fractions, but these parameters were noted to improve after operation in several patients. The remarkably high early and late survival rates, the low incidence of myocardial infarction, and the excellent functional results after rather long follow-up indicate that emergency coronary revascularization provides an effective therapy for unstable angina. The use of IMA grafts, when feasible, is a safe and possibly preferable approach in these patients.     

Vasoactive drug effects on blood flow in internal mammary artery and saphenous vein grafts

The internal mammary artery is a dynamic coronary graft, whereas the saphenous vein graft is passive. Therefore, potential exists not only for beneficial vasodilation but also for catastrophic spasm of the artery. The purpose of this study was to examine blood flow in the internal mammary and saphenous vein grafts during infusion of drugs that are commonly used after cardiac operations. A canine right heart bypass preparation allowed precise control of cardiac output, blood pressure, and heart rate, which were maintained constant during drug infusion. Both the internal mammary and saphenous vein grafts were constructed so that they perfused the same coronary bed: They were anastomosed in a Y fashion to a ligated anterior descending coronary artery. Electromagnetic flow probes measured graft flow (with the other graft occluded) before and after 15 minutes of drug infusion. The order of drug infusion was randomized and changes were compared by tests for paired differences. Phenylephrine (2 micrograms/kg/min) decreased flow in both the internal mammary and saphenous vein grafts, whereas norepinephrine (0.1 microgram/kg/min) increased flow in both grafts. Epinephrine (0.05 microgram/kg/min) increased mammary artery flow 16% +/- 6% but decreased saphenous vein graft flow 9% +/- 7%. Nitroglycerin (1 microgram/kg/min) significantly increased internal mammary flow (36% +/- 13%), from 47 +/- 7 to 59 +/- 7 ml/min (p less than 0.01), whereas flow decreased significantly in the saphenous vein graft 14% +/- 3%, from 64 +/- 9 to 59 +/- 8 ml/min (p less than 0.01). Nitroprusside (1 microgram/kg/min) decreased mammary artery flow 12% +/- 2%, from 50 +/- 7 to 44 +/- 7 ml/min (p less than 0.01), but increased saphenous vein graft flow 25% +/- 8%, from 64 +/- 9 to 77 +/- 7 ml/min (p less than 0.01). All hemodynamic variables were unchanged, except for norepinephrine, which significantly increased the first derivative of left ventricular pressure. The results suggest that flow through the canine internal mammary artery is changed by the drugs commonly used in perioperative management. Epinephrine and nitroglycerin increased internal mammary artery flow and decreased saphenous vein graft flow, whereas nitroprusside had the opposite effect. The vascular reactivity of the internal mammary artery must be considered when these drugs are used after coronary revascularization.     

Early and lage results of coronary revascularization with saphenous vein and internal mammary artery grafts.

Five hundred forty-seven consecutive coronary revascularizations for anginal syndromes and 72 combined with other procedures (valve replacement, myocardial resection, closure of septal rupture) were performed during a five year period beginning in January 1972. The 619 patients received 1,794 grafts; 208 had one or two internal mammary artery grafts (IMAG) into anterior coronary arteries with or without additional saphenous vein grafts (SVG), and 411 had SVGs only. A 99.5 per cent follow-up of eighteen to seventy-eight months (mean, 50 months) allows a balanced view of the merits and shortcomings of each conduit and an evaluation of long-term surgical results.Hospital mortality of 3.3 per cent (13 of 547) in revascularization alone included 9 deaths in 402 patients (2.2 per cent) with stable angina, 4 in 134 (3.0 per cent) with unstable angina, and 5 in 11 (45.0 per cent) with cardiogenic shock. Mortality and morbidity were similar with or without IMAGs. IMAG and SVG flows measured at operation were comparable, but one year patency was 97 per cent and 86 per cent, respectively (p < 0.05). Late occlusion (3 per cent) or “distal thread” stenosis (2 per cent) occurred only in those with small IMAGs, especially when the coronary lesion was only moderately severe. Graft occlusion and recurrence of symptoms required reoperation in five SVG and two IMAG patients. Actuarial survival was 95 per cent at one year, 93 per cent at three years, and 92 per cent at five years. Ninety-five per cent of the survivors improved one functional class (FC) or more, and 85 per cent are asymptomatic, with a higher proportion in IMAG patients. Eighty-two per cent of those less than age sixty years resumed gainful employment. Hospital mortality was higher for those with combined procedures, especially with infarctectomy and/or closure of septal rupture. Zero mortality occurred in the last two years in those with revascularization and valve replacement, perhaps related to cold cardioplegic myocardial protection.Coronary revascularization provides excellent long-term functional results. Survival in the entire group, including patients with unstable angina and those with cardiogenic shock, is significantly better than survival of patients with stable angina recently reported by the Veterans Administration Cooperative Study. A 10 per cent better long-term patency rate with an IMAG is particularly important in muscular young individuals with stable hemodynamics. Its use is not warranted in unstable patients, in patients with combined procedures, and in patients with massive left ventricular hypertrophy.     

Nitric oxide and cyclic guanosine monophosphate stimulate apoptosis via activation of the Fas-FasL pathway.

BACKGROUND: Inappropriately exaggerated response of pulmonary vascular cells to inflammatory mediators may be one mechanism that leads to acute (or adult) respiratory distress syndrome. Nitric oxide (NO) is induced following such exaggerated responses and may have a variety of biological effects, including induction of apoptosis. The mechanism by which NO causes apoptosis is unknown; however, Fas (CD95) and Fas ligand (FasL) (CD95L) have been implicated. We hypothesized that NO-induced apoptosis in pulmonary vascular smooth muscle cells is mediated through a Fas-FasL pathway. MATERIALS AND METHODS: Cultured human and rat pulmonary artery smooth muscle cells (PASMCs) were exposed to soluble FasL (0-5 ng/ml), the NO donor S(G)-nitroso-N-acetyl pencillamine (SNAP) (0-50 microg/ml), and/or anti-FasL (0-100 microg/ml) for 12 h. Apoptosis was measured using in situ DNA nick end labeling and flow cytometry. Changes in Fas and FasL protein levels were assessed via Western blot analysis. Messenger RNA (mRNA) abundance of apoptosis-related genes was determined using a ribonuclease protection assay. RESULTS: Rat PASMCs exposed to FasL show a dose-dependent increase in apoptosis. Human PASMCs are less responsive to FasL. Addition of anti-FasL to rat PASMCs treated with 10(-5) M SNAP decreases apoptosis levels compared to SNAP treated alone. FasL and Fas receptor proteins are increased in response to 10(-3) to 10(-4) M SNAP or 10(-6) M 8-bromo-cyclic guanosine monophosphate (cGMP). The mRNA abundance of Fas, FasL, and other apoptosis-related genes is increased in response to 10(-6) M 8-bromo-cGMP but not 8-bromo-cyclic adenosine monophosphate. CONCLUSIONS: Nitric oxide-induced apoptosis in rat and human PASMCs is mediated, at least in part, through the Fas-FasL pathway, with cGMP increasing the expression of Fas and FasL.     

Natriuretic peptide responsive, cyclic guanosine monophosphate producing structures in the guinea pig bladder

PURPOSE: We examined the localization of natriuretic peptide responsive, cyclic guanosine monophosphate producing cells in the guinea pig bladder. MATERIALS AND METHODS: The bladder was removed from male guinea pigs sacrificed by cervical dislocation. The lateral wall of the bladder was cut into strips 2 mm thick. The tissue pieces were incubated in the presence of human atrial natriuretic peptide, rat brain natriuretic peptide and C-type natriuretic peptide or the nitric oxide donor DEANO (diethylamine NONOate or 1,1-diethyl-2-hydroxy-2-nitrosohydrazine) (Sigma). Cyclic guanosine monophosphate immunoreactivity was localized using an antibody against formaldehyde fixed cyclic guanosine monophosphate. RESULTS: Atrial natriuretic peptide and brain natriuretic peptide stimulated cyclic guanosine monophosphate synthesis in suburothelial interstitial cells, whereas C-type natriuretic peptide was not effective. In contrast, DEANO stimulated cyclic guanosine monophosphate synthesis in urothelial umbrella cells, suburothelial interstitial cells, muscle interstitial cells and neurons. The effect of atrial natriuretic peptide and brain natriuretic peptide was not inhibited by ODQ (1H-[1, 2, 4]oxadiazolo[4-3a]quinoxalin-1-one), an inhibitor of nitric oxide responsive soluble guanylyl cyclase. CONCLUSIONS: To our knowledge our findings show for the first time a localized effect of atrial natriuretic peptide and brain natriuretic peptide to the suburothelial cells of the guinea pig bladder. These cells express the soluble guanylyl cyclase and particulate guanylyl cyclase-A isoforms. The specific physiological role of these cells is not known but it was suggested that they may be involved in the generation or modulation of sensation. The results imply a role for natriuretic peptide-cyclic guanosine monophosphate signaling in the processing of sensory information in the bladder.     

Effects of vasoactive drugs on flows through left internal mammary artery and saphenous vein grafts in man.

Vasoactive agents are commonly used in the postcardiopulmonary bypass period to elevate the mean arterial pressure of myocardial revascularization patients. Concern exists that administration of vasoactive agents in this setting may affect flow through saphenous vein and internal mammary artery grafts. Twenty-eight patients were randomly assigned to receive one of the six two-drug combinations of phenylephrine, norepinephrine, and epinephrine. After termination of cardiopulmonary bypass baseline, hemodynamic measurements and electromagnetic flow probe measurements of saphenous vein and internal mammary artery graft flow were made. The first agent was then infused to elevate mean arterial pressure 20 mm Hg. After 5 minutes of stability, hemodynamic and graft flow measurements were repeated. The infusion was terminated, 5 minutes of stability were obtained, and baseline measurements were repeated. The second agent was then infused, and measurements were repeated after a 5-minute stabilization period. Phenylephrine induced a nonsignificant increase in saphenous vein graft flow (68 +/- 31 versus 81 +/- 49 ml/min) and a significant decrease in internal mammary artery graft flow (40 +/- 16 versus 32 +/- 12 ml/min). Norepinephrine induced a significant increase in saphenous vein graft flow (80 +/- 39 versus 97 +/- 39 ml/min) and no significant change in internal mammary artery graft flow (44 +/- 20 versus 45 +/- 20 ml/min). Epinephrine induced a significant increase in both saphenous vein (82 +/- 38 versus 96 +/- 40 ml/min) and internal mammary artery (38 +/- 12 versus 55 +/- 24 ml/min) graft flows. We conclude that administration of vasoactive agents in the postcardiopulmonary bypass period may significantly affect saphenous vein and internal mammary artery graft flows.     

Blood flow velocity of internal mammary artery and saphenous vein grafts to the coronary arteries

Doppler-derived blood flow velocity measurements were used to characterize the hemodynamics of 66 internal mammary artery grafts and 60 saphenous vein grafts to the coronary arteries at operation. Pulsed Doppler spectral analysis of centerstream graft flow demonstrated predominantly diastolic flow with a variable, multiphasic flow pattern in systole. The magnitude and configuration of the graft flow velocity waveform varied with graft type and whether the runoff was to single or multiple arteries. At operation, peak diastolic flow velocity was greater (P less than 0.0001) in internal mammary artery grafts to a single outflow artery (71 +/- 2 cm/sec) compared with single vein grafts (31 +/- 4 cm/sec). Sequential grafts demonstrated increased flow velocity and forward flow throughout the pulse cycle, indicative of low outflow resistance. Analysis of the phasic flow patterns permitted an assessment of functional graft patency. Technical errors (anastomotic stricture, internal mammary pedicle torsion) were identified in three grafts with low or absent diastolic flow. Vasospasm of the internal mammary artery was associated with high flow velocity throughout the pulse cycle. Observed differences in patency and the development of intimal hyperplasia between internal mammary artery and saphenous vein grafts may be related to graft hemodynamics.     

Comparative study of aorto-coronary bypass surgery using internal mammary artery grafts and saphenous vein grafts

From April, 1985, through March, 1988, 202 patients had aorto-coronary artery bypass (CABG). In two series of consecutive patients who underwent CABG alone with the saphenous vein (SVG) or the internal mammary artery (IMA), mortality, morbidity and postoperative angiographic findings were compared with two series. The mean number of grafts placed was 1.8 per patient (1 to 4 grafts) in IMA group and 2.2 per patient (1 to 4 grafts) in SVG group. Mortality was 3% in two groups. The intraoperatively mean blood flow of graft to LAD in SVG and the mean blood flow of free end of IMA had no significant difference. The early patency rate (1.5 months) was 96% for 177 grafts in IMA group, 97% for 100 with IMA-LAD anastomosis, and 95% for 221 grafts in SVG group, 97.7% for 88 with SVG-LAD anastomosis. Morbidity was not significantly different. Many reports suggested that the long-term patency rate was good within the IMAG. In conclusion, the usefulness of IMAG in Japanese patients should be more stressed in young patients.     

The impairment of endothelium-dependent relaxations in reversed vein grafts is associated with a reduced production of cyclic guanosine monophosphate.

The present study investigated the underlying mechanisms associated with the loss of responsiveness of veins grafted into the arterial circulation. In particular, the possibility that the altered response is related to modifications of the biologic properties of the vascular smooth muscle, of the endothelial cells or both was tested. Segments of jugular veins were grafted in the reverse position into the carotid arteries in rabbits. After 4 weeks the patent vein grafts and unoperated veins were removed, and endothelium-dependent (acetylcholine) and endothelium-independent (nitric oxide, SIN-1 [the active metabolite of molsidomine32]) relaxations were studied in vitro. In unoperated veins, acetylcholine, nitric oxide, and SIN-1 induced a concentration-dependent relaxation in the presence and absence of the endothelium, respectively. These relaxations were associated with a time-dependent accumulation of guanosine 3':5'-cyclic monophosphate (cyclic GMP). Both relaxation and production of cyclic GMP were inhibited by methylene blue and hemoglobin. Unstimulated veins with endothelium had a significantly higher content of cyclic GMP than did preparations without endothelial cells. This difference was abolished by hemoglobin and methylene blue. In vein grafts acetylcholine induced only minor endothelium-dependent relaxations, whereas nitric oxide and SIN-1 evoked concentration-dependent relaxations in preparations without endothelium, which were shifted significantly to the right compared to unoperated veins. In vein grafts the endothelium-mediated production of cyclic GMP (basal and stimulated by acetylcholine) was significantly reduced when compared to that in unoperated veins, and that evoked by SIN-1 was not different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multivessel coronary revascularization without saphenous vein: long-term results of bilateral internal mammary artery grafting

When the saphenous vein is absent or inadequate, options for multivessel coronary revascularization include bilateral mammary artery grafting and the use of conduits of unproven durability (arm vein, homologous umbilical vein, prosthetic graft). To evaluate the long-term effectiveness of bilateral mammary artery grafting, we reviewed the cases of 76 consecutive patients with multivessel disease (33 with two-vessel disease, 43 with three-vessel disease) who underwent revascularization with bilateral mammary artery grafts only during the period from 1971 to 1980. No hospital deaths occurred. Thirty-three free and 119 in situ grafts were used. Late follow-up was complete, ranging from 12 to 132 months (mean interval, 67 months) and revealed improvement by at least one New York Heart Association functional class in 59 of 71 survivors. Postoperative arteriograms (mean interval, 26 months) of 55 grafts in 28 patients showed that 49 grafts were patent (89%). Five late deaths (2 noncardiac) occurred. Actuarial survival was 97.2% to seven years and 90.2% at nine years after operation. Bilateral mammary artery grafting yielded excellent graft patency, relief of symptoms, and long-term survival. When saphenous vein is unsuitable for grafting, bilateral mammary artery grafts should be utilized before other conduits are considered.     

A comparative study on in vitro and in vivo effects of topical vasodilators in human internal mammary, radial artery and great saphenous vein

Objective: As an important prognostic factor of coronary artery bypass grafting (CABG), graft vasospasm can be observed in all currently used graft conduits. Radial artery (RA) vasospasm is more prone to occur in comparisons with internal mammary artery (IMA) and great saphenous vein (GSV). There is still controversy about which antispasmodic agent is superior to different grafts, especially to RA conduits. The aim of this pilot study was to investigate the relaxation response of four topical vasodilators to different in vitro grafts and how these vasodilators affect the blood flow of the vessel in situ during RA harvesting. Materials and methods: Vasodilatory properties of diltiazem, nitroglycerin, urapidil and nicorandil were compared in matched patient-specific segments of RA, IMA and GSV harvested from 12 patients. The vasodilatory response of the RA to intraradial administration of nitroglycerin, diltiazem and urapidil was compared in vivo (n=10 per group) by assessing the free blood flow of RA. Results: (1) The maximal relaxations occurring with urapidil, nitroglycerin and nicorandil in IMA, RA and SGV were significantly greater than that with diltiazem. The reactivity of all three graft conduits showed similar relaxation with nitroglycerin or with diltiazem, but the relaxation with urapidil in RA showed greater than that of IMA and GSV, and RA and GSV showed greater relaxation with nicorandil than IMA. (2) A dose of 10(-5)mol/l of nitroglycerin, urapidil and nicorandil but not diltiazem significantly inhibited the RA response to PE. (3) In vivo, urapidil and nitroglycerin significantly increased the RA blood flow, the potency of which was greater than that caused by diltiazem. Conclusions: (1) Comparing with nicorandil, urapidil and diltiazem, nitroglycerin caused a significant relaxation in all three graft vessels tested. (2) Nitroglycerin, nicorandil and urapidil were more effective in preventing RA spasm than diltiazem.