Biomedical subjects

E Svendsen

Publications and source records attributed to E Svendsen.

At least 37 records · Page 2Linked to original sources

PubMed1996

Balloon catheter injury and vein graft morphology and function.

Endovascular interventions to salvage failing vein bypass grafts are often associated with suboptimal outcomes. This study examines the effect of experimental vein graft catheter injury on vein graft morphology and vasomotor function. Thirty New Zealand white rabbits underwent a right common carotid interposition vein bypass graft. Ten grafts were harvested at 14 days, 10 were harvested at 28 days, and 10 had a balloon catheter injury induced at 14 days (4 F Fogarty catheter, 0.6 to 0.75 ml water inflation, 3 passes) and these 10 grafts were harvested after an additional 14 days. Morphologic and morphometric determinations (n = 5) or in vitro contractile studies (n = 5) were performed on segments of the vein grafts. Intimal thickness, without any intervention, increased by 84% from 14 to 28 days (p < 0.01), whereas catheter injury at 14 days induced a twofold increase (p < 0.001) in the formation of intimal hyperplasia by 28 days. Scanning electron microscopy demonstrated near-complete endothelial denudation after balloon catheter injury. In the 14- and 28-day control vein grafts, and in the balloon-injured vein grafts, the vascular surfaces had confluent endothelial linings. However, the ultrastructural features of the endothelial cells were group specific. Transmission electron microscopy of the same specimens confirmed this. There were no significant differences in contractility between the 28-day control and the catheter-injured vein grafts. This study demonstrates that balloon catheter injury doubles the rate at which intimal hyperplasia develops in vein grafts without significantly altering the physiologic phenotype of the smooth muscle cells as defined by their vasomotor function.

Animals↗

PubMed1996

A comparative study of endothelium-derived relaxing factor-mediated relaxation and smooth muscle cell function in arterial and venous vein bypass grafts.

The development of intimal hyperplasia in reversed vein grafts is associated with altered endothelial and vasomotor function. This study examines the effect of surgery on the morphology and vasomotor function of experimental arterial and venous vein bypass grafts. Twelve reversed vein grafts, 12 in situ vein grafts and 12 venovenous grafts were placed in 24 New Zealand White rabbits. All grafts remained patent and were harvested after 28 days. Isometric contraction to norepinephrine, histamine, bradykinin, serotonin and relaxation to acetylcholine and sodium nitroprusside following pre-contraction with prostaglandin F(2 alpha) were determined on the grafts and on contralateral jugular veins. Compared to the contralateral jugular veins, norepinephrine supersensitivity was induced in the reversed vein grafts, and venovenous vein grafts but not in the in situ vein grafts. Decrease in histamine sensitivity occurred in all grafted vessels. Bradykinin responses were significantly reduced in the in situ vein grafts and reversed vein grafts. Contractile responses to serotonin developed in the in situ vein grafts and reversed vein grafts only. Acetylcholine-induced endothelium-derived relaxing factor-mediated relaxation of the contralateral jugular veins was preserved in both venovenous grafts and in situ vein grafts but was lost in reversed vein grafts. All tissues relaxed to sodium nitroprusside in dose-dependent manner. The data suggest that norepinephrine supersensitivity in reversed vein grafts results from excision of the vessel. Attenuation of bradykinin responses and the enhanced contractile responses to serotonin appear predominantly to result from arterialization. Decreases in histamine sensitivity appear related both to excision and to arterialization. Neither the excision of the vein nor arterialization individually influences the alterations in endothelium-derived relaxing factor-mediated relaxation. However, a combination of excision and arterialization results in the altered endothelium-derived relaxing factor-mediated relaxation. This study suggests that the surgical preparation of the vein and the surgical procedure used have significantly different effects on endothelium-derived relaxing factor-mediated relaxation and smooth muscle contractility in vein grafts.

Acetylcholine↗

PubMed1996

Suppression of intimal hyperplasia in experimental vein grafts by oral l-arginine supplementation and single ex vivo immersion in deferoxamine manganese.

PURPOSE: Vein grafts undergo morphologic and functional changes after insertion into the arterial circulation with the development of intimal hyperplasia, as well as significant alterations in endothelial and smooth muscle cell physiologic responses. METHODS: Forty New Zealand white rabbits underwent jugular vein interposition grafting of the common carotid artery. Ten animals were controls, 10 animals received 2.25% L-arginine supplementation in their drinking water (200 ml/day; 2 gm/kg) 7 days before surgery and continued thereafter until harvest, in 10 animals the veins were immersed in deferoxamine manganese (DFMn; 10(-3) mol/L in heparinized Ringer's lactate for 15 minutes) before implantation, and 10 received both L-arginine supplementation and either histologic (n=6) or isometric tension studies (n=4). The function of the vein grafts was compared with that of jugular veins. RESULTS: Treatment with DFMn, l-arginine, amd DFMn L-arginine produce increases in mean intimal thickness of 39% (51 +/ -7 microm; p<0.05), 51% (41 +/- 7 microm; p<0.05), and 65% (29 +/- 6 microm; p< 0.01), respectively, compared with control vein grafts (83 +/- 12 microm). Compared with the control group, the intimal ratio ([intima]/[intima + media]) decreased by 16% (difference not significant), 8% (difference not significant), and 47% (p<0.01) in the DFMn-, L-arginine- and and DFMn/L-arginine-treated vein grafts, respectively. Jugular veins relaxed to acetylcholine (53% +/- 12% maximal relaxation), whereas control vein grafts did not relax. In contrast, vein grafts from each of the experimental groups relaxed to acetylcholine with maximal relaxations of 26% +/- 7% (p<0.05 compared with the jugular vein), 22% +/- 8% (p<0.05), and 44% +/- 14% (difference not significant) in the DFMn, L-arginine, DFMn/L-arginine groups, respectively. Neither DFMn nor l-arginine had a significant effect on the alterations in smooth muscle contractility that occur in control vein grafts. CONCLUSION: This study demonstrates that an agent that modulates free radical production combined with a precursor of nitric oxide formation will lead to a significant decrease in the formation of intimal hyperplasia in arterial vein grafts with the preservation of endothelial-derived relaxation.

Administration, Oral↗

PubMed1996

Characterisation of angiotensin II receptor mediated responses and inhibition of intimal hyperplasia in experimental vein grafts by the specific angiotensin II receptor inhibitor, L158,809.

OBJECTIVES: This study characterises pharmacologically the angiotensin II receptor in experimental vein grafts and examines the effect of the angiotensin II receptor (type 1) antagonist (L158,809) on the formation of vein graft intimal hyperplasia in vivo, as well as the in vitro physiological response to angiotensin II of vein grafts after chronic oral L158,809 treatment. MATERIALS: Thirty New Zealand White rabbits had a right carotid interposition bypass graft using the external jugular vein and were killed on the 28th postoperative day. DESIGN: To characterise the angiotensin II receptors, concentration response curves to angiotensin II were obtained in vitro in the presence or absence of L158,809. To determine the effect of L158,809 on the development of intimal hyperplasia, 10 animals received chronic oral therapy with L158,809 (10 mg/kg/day; begun 5 days before surgery and continued until harvest) and 10 animals received vehicle only as controls. These grafts were harvested either for histology (n = 6 per group) or for in vitro isometric tension studies to angiotensin II. RESULTS: The monophasic contractile response to angiotensin II in the untreated vein grafts could be inhibited in a concentration dependent manner by L158,809 with first order kinetics. Chronic oral treatment with L158,809 produced a 48% decrease in intimal thickness from 82 +/- 1 micron (mean +/- S.E.M.) in the controls to 43 +/- 7 microns in the treated vein grafts (p = 0.002). There was also a significant decrease (45%) in the medial thickness between the control (76 +/- 6 microns) and L158,809 treated (42 +/- 6 microns) vein grafts (p = 0.007). The responses to angiotensin II were abolished in the vein grafts by chronic L158,809 therapy. CONCLUSIONS: This study suggests that vein graft angiotensin II responses are mediated through a type 1 receptor and that chronic inhibition with L158,809, significantly reduces intimal hyperplasia and medial hypertrophy in experimental vein grafts and concomitantly abolishes the in vitro responses to angiotensin II. Therefore, angiotensin II acting through AT1 receptors mediates a significant part of the intimal hyperplastic response in vein grafts.

Angiotensin II↗

PubMed1995

Control of accelerated vein graft atheroma with the nitric oxide precursor: L-arginine.

Hyperlipidemia contributes to the development of intimal hyperplasia and subsequent accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary supplementation with L-arginine on the development of intimal hyperplasia and the vasomotor function of vein grafts in hypercholesterolemic animals. Thirty male New Zealand White rabbits had a right carotid vein bypass graft and were sacrificed at 28 days postoperatively. Twenty animals received a 1% cholesterol diet for 4 weeks prior to surgery and this diet was continued until harvest. Of these, 10 also received L-arginine (2.25%, 2 g/kg, p.o.) 7 days preoperatively and thereafter until harvest. The last 10 animals were controls. Vein grafts were harvested either for morphology or for in vitro isometric tension studies. Cumulative dose-response curves to norepinephrine, serotonin, and bradykinin were recorded, and following norepinephrine precontraction, relaxation to acetylcholine and sodium nitroprusside were determined. After in situ pressure fixation, intimal thicknesses of the vein grafts were measured by videomorphometry. The addition of L-arginine doubled the serum arginine concentrations. Intimal hyperplasia of both groups of hypercholesterolemic vein grafts contained foam cells and lipid-laden endothelial and smooth muscle cells. There was a 24% reduction in the intimal thickness of vein graft intimal hyperplasia in the L-arginine group compared to that in the hypercholesterolemia group (P < 0.05). All hypercholesterolemic vein grafts were two-fold thicker than in the control group. L-arginine supplementation resulted in the preservation of acetylcholine-mediated relaxation but did not change hypercholesterolemia-induced contractile agonist supersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Dilation of the internal mammary artery by external and intraluminal papaverine application.

Three methods for prevention of perioperative spasm of the internal mammary artery were compared in 78 patients undergoing coronary artery bypass grafting. In group 1, internal mammary artery pedicles were divided distally, clamped, and placed under the upper sternum submerged in papaverine solution (1.5 mg/ml). In group 2, as in group 1 but before clamping, 2 ml of heparinized blood with 1.5 mg/ml papaverine added was injected into the vessel lumen. In group 3 treatment was as in group 2, but heparinized blood with papaverine was injected a second time just before extracorporeal bypass was begun. In a univariate analysis free flow from dilated internal mammary arteries was not significantly different among the groups (group 1, 58 ml/min; group 2, 82 ml/min; group 3, 68 ml/min; p < 0.1). When free flow from dilated internal mammary arteries was the dependent variable in a regression analysis, the use of intraluminal papaverine, high blood pressure during flow measurement, and high initial blood flow were predictors of high flow (all p < 0.01). Morphometric measurements on the resected distal portion of the dilated internal mammary arteries disclosed less folding of the internal elastic lamina and a larger luminal area in groups 2 and 3 compared with respective findings in group 1 (1.21 mm2 and 1.42 mm2 versus 0.77 mm2; p < 0.02). Mechanical vessel wall injury occurred in 8 of 52 internal mammary arteries treated with intraluminal papaverine. Intraluminal papaverine solution injected once or twice in addition to external papaverine exposure therefore provides a better blood flow rate and distal dilation than mere submersion in papaverine solution, but at a considerable risk of mechanical wall injury.

Adult↗

PubMed1995

The influence of the combined presence of diabetes mellitus and hypercholesterolaemia on the function and morphology of experimental vein grafts.

OBJECTIVES: Diabetes and hypercholesterolaemia are known risk factors for the development of atherosclerosis and are considered to influence the development of vein graft intimal hyperplasia. This study examines the combined effect of diabetes for 12 weeks (alloxan-induced) and hypercholesterolaemia for 8 weeks (1% cholesterol diet) on the formation of intimal hyperplasia and the vasomotor function of vein grafts. MATERIALS AND DESIGN: Thirty-two New Zealand White rabbits underwent a carotid vein bypass graft. Eight were controls, eight were diabetic, eight were hypercholesterolaemic and eight had both diabetes and hypercholesterolaemia. All vein grafts were harvested at 4 weeks postoperatively for morphology (n = 4) or contractility studies (n = 4). RESULTS: Compared to controls, both diabetes and hypercholesterolaemia increased intimal thickness by 20% and 63% respectively; medial thicknesses of these vein grafts were unchanged compared to control. In contrast, diabetes with hypercholesterolaemia dramatically increased intimal and medial thickness (1.8 fold and 1.6 fold respectively, compared to control). Smooth muscle cell contractility was enhanced in both the diabetic and hypercholesterolaemic groups. The presence of diabetes with hypercholesterolaemia did not further alter the enhanced smooth muscle cell contractile responses. CONCLUSIONS: This study suggests that the combination of both the atherogenic risk factors, hypercholesterolaemia and diabetes, significantly augments the formation of intimal hyperplasia in experimental vein grafts.

Animals↗

PubMed1995

Ramipril and experimental vein graft intimal hyperplasia.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the intimal proliferation in animal models of arterial angioplasty and vein bypass grafting. This study examines the effect of high-dose ramipril, an ACE inhibitor that does not contain a sulfhydryl group, on the development of intimal hyperplasia in experimental vein bypass grafts. Twenty New Zealand White rabbits underwent common carotid interposition bypass grafting. Twelve were treated with ramipril (2 mg/kg/day; po) five days prior to surgery and thereafter until harvest. The remaining 8 animals were used as controls. Vein grafts were harvested at twenty-eight days by pressure fixation (80 mmHg). The grafts were sectioned into proximal, middle, and distal thirds, and the thickness of the intima and the media and the area of the lumen from each segment were determined by videomorphometry. The effect of ramipril on the [H3]thymidine incorporation into DNA of serum-stimulated smooth muscle cells (culture passage 6 to 12) was also assessed. There was a 50% mortality rate in the rabbits that received ramipril, and this was assumed to be related to the high dose of the drug. Ramipril treatment reduced mean vein graft intimal area by 34% (P > 0.05), but this was accompanied by an increase of 73% in the mean medial area of the vein grafts as compared with controls. These changes resulted in a decrease in the mean intimal ratio (intima/[intima + media]) by 39% in the ramipril group as compared with controls. Ramipril did not inhibit [H3]thymidine incorporation into DNA of serum-stimulated smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Systemic hypertension and hypercholesterolemia in vein grafts: effects on the function and morphology of experimental vein grafts.

Hypertension and hypercholesterolemia are known risk factors for the development of atherosclerosis and are considered to influence the development of vein graft intimal hyperplasia. This study examines the effect of hypertension (two-kidney, one-clip model for 8 weeks) and hypercholesterolemia (1% cholesterol diet for 8 weeks) individually and in combination on the formation of intimal hyperplasia and the vasomotor function of vein grafts. Forty New Zealand White rabbits underwent a carotid vein bypass graft. Ten were controls, 10 were hypertensive, 10 were hypercholesterolemic, and 10 had both hypertension and hypercholesterolemia. Hypertension and/or hypercholesterolemia were present for 4 weeks prior to and for 4 weeks after surgery. All vein grafts were harvested at 4 weeks postoperatively for histology (n = 6) or contractility studies (n = 4). Compared to controls, hypercholesterolemia increased intimal but not medial thicknesses of the vein grafts and enhanced smooth muscle cell contractility. Hypertension did not increase vein graft intimal or medial thicknesses but did augment vein graft contractility compared to controls. Hypertension with hypercholesterolemia increased intimal and medial thicknesses and enhanced vasoreactivity in vein grafts. The results show that hypertension influences the vasoreactivity but not the development of intimal hyperplasia in vein grafts. When hypertension is combined with hypercholesterolemia, there is both an increase in the medial thickness and an attenuation of vasomotor function compared to hypercholesterolemia alone, although there is no further increase in intimal hyperplasia formation. Therefore, this study suggests that the combination of both atherogenic risk factors does not act synergistically in promoting either the formation of intimal hyperplasia or vasomotor dysfunction in vein grafts.

Animals↗

PubMed1994

The functional and morphological consequences of balloon catheter injury in veins.

Endovascular procedures are now used to treat occlusive arterial and venous diseases. However, after arterial catheter injury, intimal hyperplasia develops and there is altered endothelial and smooth muscle cell vasoreactivity of the vessel segment. This study examines the morphology and vasoreactivity of veins which have undergone balloon catheter injury. Under direct vision, 22 jugular veins of 11 New Zealand White rabbits were catheterized with a Fogarty balloon catheter (4Fr, three passes, 0.75 ml H2O inflation). Ten uninstrumented jugular veins from 5 additional animals were used as controls. Immediately after balloon injury, 10 jugular veins were harvested. Scanning electron microscopy of these vessels confirmed complete endothelial denudation and no in vitro endothelium-dependent relaxation was observed. After 28 days, 12 veins were harvested. There were no occlusions. Histologically, the 28-day balloon-injured veins had an almost confluent endothelium. However, there was medial hypertrophy but no development of intimal hyperplasia. There were no significant changes in the contractile responses of the balloon-injured veins after 28 days to norepinephrine. Bradykinin and histamine responses were markedly attenuated. Following bradykinin precontraction, balloon-injured veins showed diminished acetylcholine sensitivity with a reduced maximal response, and a small decrease in serotonin sensitivity with a markedly decreased maximal response. In contrast, there was an increased sensitivity in response to sodium nitroprusside without a change in maximal response in precontracted balloon-injured veins. This study shows that after 28 days venous balloon injury does not induce the development of intimal hyperplasia but does reduce overall endothelial dependent relaxation (acetylcholine- and serotonin-mediated) with increased sensitivity to endothelial independent relaxation (sodium nitroprusside-mediated). These findings would suggest that when compared to arterial balloon injury, venous balloon injury does not carry the same histological and vasoconstrictive sequelae but does demonstrate similarly impaired endothelial cell function.

Animals↗

PubMed1994

Experimental hypercholesterolemia in rabbits induces cavernosal atherosclerosis with endothelial and smooth muscle cell dysfunction.

Hypercholesterolemia and other vascular risk factors for atherosclerosis are commonly associated with impotence. To characterize cavernosal smooth muscle reactivity in hypercholesterolemia, we performed isometric tension studies (with norepinephrine, acetylcholine, papaverine and electrical field stimulation) on isolated strips of corpus cavernosum from rabbits fed a 1% cholesterol diet. To assess the impact of cholesterol reduction, a group of rabbits was fed a cholesterol diet for 4 weeks and was then returned to a normal diet for 4 weeks before testing. Potential structure-function relationships were delineated by ultrastructural evaluation with transmission electron microscopy (TEM). All forms of cavernosal relaxation, including papaverine relaxation, were impaired with hypercholesterolemia, and norepinephrine contraction was augmented. In addition, ultrastructural evidence of an early atherosclerotic process in the cavernosal sinusoids was detected. Importantly, reduction of elevated serum cholesterol normalized cavernosal relaxation, including that of papaverine, and decreased the sensitivity to norepinephrine, thereby suggesting that cavernosal smooth muscle dysfunction in hypercholesterolemia is reversible.

Animals↗

PubMed1994

Diabetes mellitus and experimental vein graft structure and function.

PURPOSE: Diabetes mellitus is a known risk factor for accelerated atherosclerosis and for postangioplasty restenosis. METHODS: This study examines the effect of chronic, uncontrolled, alloxan-induced diabetes on the structure and vasomotor function of vein bypass grafts in 20 male New Zealand white rabbits with diabetes and in 10 controls. After 8 weeks of diabetes, a common carotid vein bypass graft was performed. Four weeks after operation, vein grafts and contralateral jugular veins were harvested. RESULTS: Diabetes induced a twofold increase in the vein graft intimal thickness compared with control. There was no change in medial thickness. Electron microscopy of the vein grafts in diabetes revealed intercellular gaps in the endothelium lining and abnormal endothelial cell junctions compared with controls. Diabetes significantly increased the maximal contractions generated in vein grafts to all contractile agonists tested without any change in sensitivity. CONCLUSIONS: This study demonstrates that diabetes alters endothelial cell structure and increases the development of intimal hyperplasia with increased maximal contractility in vein grafts and therefore suggests that the vein grafts in diabetes are more susceptible to early stenosis.

Animals↗

PubMed1994

Control of the structural and functional consequences of vein graft intimal hyperplasia with a 21-aminosteroid--U74389G.

Following angioplasty and vein bypass grafting, there is endothelial cell injury, infiltration of leukocytes and smooth muscle cell (SMC) proliferation leading to intimal hyperplasia which may result in stenosis and can lead to eventual occlusion. This study examines the effect of the 21-aminosteroid U74389G (Upjohn Company), on the formation of vein graft intimal hyperplasia in vivo and on SMC DNA synthesis and proliferation in vitro. Twenty New Zealand White rabbits had a right carotid interposition bypass graft using the ipsilateral external jugular vein. Ten animals received chronic oral therapy with U74389G (25 mg/kg/day; begun 5 days before surgery and continued until harvest) and 10 control animals received vehicle only. All animals were sacrificed on the 28th postoperative day. Vein grafts were harvested either for histology/videomorphometry (n = 6 per group) or for in vitro isometric tension studies (n = 4; four 5 mm rings per graft). The incorporation of [3H]thymidine into the cellular DNA of serum-stimulated rabbit aortic SMC (passage 6th to 12th) was assessed in the presence of increasing concentrations of U74389G (10(-9) to 10(-4) M). The effect of U74389G on in vitro cell proliferation was also assessed. Treatment with U74389G produced a 44% decrease in overall mean intimal thickness from 82 +/- 1 microM (mean +/- S.E.M.) in the controls to 57 +/- 10 microM in the U74389G treated vein grafts (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Postoperative reduction of high serum cholesterol concentrations and experimental vein bypass grafts. Effect on the development of intimal hyperplasia and abnormal vasomotor function.

Hypercholesterolemia is an important contributor to the development of intimal hyperplasia and superimposed accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary modification of serum cholesterol on the development of intimal hyperplasia and vasomotor function of vein grafts. Thirty male New Zealand White rabbits had a right carotid vein bypass graft and were put to death 28 days after the operation. Twenty animals received a 1% cholesterol diet for 4 weeks before the operation. In 10 animals this diet was continued until harvest (hypercholesterolemia group). In another 10 animals the diet was changed to standard rabbit chow on the day of the surgical procedure and continued until harvest (cholesterol reduction group). The last 10 animals were control subjects. Vein grafts were harvested either for histologic study or for in vitro isometric tension studies. Cumulative dose response curves to norepinephrine, serotonin, bradykinin, and endothelin-1 were determined. After in situ pressure fixation, intimal thicknesses of the vein grafts were measured by videomorphometry. The change in diet produced a 74% reduction in serum cholesterol concentration within 28 days. There was a 26% reduction in the intimal thickness of vein graft intimal hyperplasia and the macroscopic disappearance of atheromatous lesions from the graft wall, which are always observed in vein grafts from the hypercholesterolemia group. Cholesterol reduction did not change hypercholesterolemia-induced agonist supersensitivity. Therefore, cholesterol reduction slows the formation of intimal hyperplasia in vein grafts but does not prevent the persistence of the hypercholesterolemia-associated smooth muscle phenotype.

Animals↗

PubMed1994

Reduction of experimental vein graft intimal hyperplasia and preservation of nitric oxide-mediated relaxation by the nitric oxide precursor L-arginine.

BACKGROUND: Previous studies in animals and human beings have shown that vein bypass grafts exhibit diminished endothelium-dependent relaxation and the development of intimal hyperplasia. This study examines the effect of L-arginine on experimental vein graft endothelial cell function and the development of intimal hyperplasia. METHODS: Common carotid vein bypass grafts were performed in 24 New Zealand White rabbits: 12 were controls and 12 received L-arginine (2.25%) orally 7 days before operation and thereafter until harvest 28 days after operation. Intimal and medial dimensions were determined by planimetry on pressure-fixed vessels. Relaxation to acetylcholine, serotonin, calcium ionophore (A23187), and sodium nitroprusside was performed on precontracted vessel rings. RESULTS: Arginine-treated vein grafts showed a 47% reduction in mean intimal thickness (p < 0.001) compared with controls. By scanning and transmission electron microscopy, all vein grafts showed a confluent endothelium. In contrast to control grafts, which do not relax to acetylcholine and serotonin, arginine-treated vein grafts relaxed in response to both agonists. There was a significant increase (p < 0.05) in the maximal relaxation to calcium ionophore (A23187) in arginine-treated vein grafts compared with control grafts. Non-endothelium-dependent responses to sodium nitroprusside were equivalent in all vein grafts. CONCLUSIONS: This study shows that oral L-arginine supplementation significantly reduces intimal hyperplasia and preserves nitric oxide-mediated relaxation in experimental vein grafts, suggesting a role for nitric oxide in the regulation of the cellular events that lead to intimal hyperplasia.

Animals↗

PubMed1993

Hypercholesterolemia and experimental vein grafts: accelerated development of intimal hyperplasia and an increase in abnormal vasomotor function.

Hypercholesterolemia is an important risk factor for the development of atherosclerosis. Late vein graft failure has been attributed to a combination of both intimal hyperplasia and atherosclerosis. This study examines the effect of hypercholesterolemia on the early morphology and vasomotor function of experimental vein grafts. Forty New Zealand White rabbits received either a 1% cholesterol diet (n = 24; HC) or a standard diet (n = 16; CON) for 4 weeks before operation and thereafter until harvest. All animals underwent a reversed vein common carotid artery bypass. The vein grafts and contralateral veins were harvested at 2 and 4 weeks after operation in both groups for either histological and morphometric analysis (n = 8 for each group) or for in vitro isometric tension studies using serotonin (5-HT), norepinephrine (NE), bradykinin (BK), and endothelin-1 (ET) and following NE precontraction, relaxation in response to acetylcholine (ACh) and sodium nitroprusside (SNP). Serum cholesterol levels were measured after 4, 6, and 8 weeks of the cholesterol diet. Serum cholesterol concentrations were 20 to 30 times higher than controls in the hypercholesterolemic animals at all times. The intimal area of the grafts in the HC group increased by twofold at 2 weeks and threefold at 4 weeks compared to corresponding controls. In contrast to the CON vein grafts, the intima of the vein grafts from HC consisted mainly of lipid-laden smooth muscle cells with scattered interspersed macrophages and occasional lipid plaques between the intima and the media. Medial areas were similar in all grafts. HC grafts became progressively more sensitive to 5-HT at 2 and 4 weeks. A supersensitivity to NE and BK developed at 4 weeks in HC grafts. There was no change in sensitivity to ET. While no graft relaxed to ACh, HC grafts contracted at low doses. All grafts responded to SNP in a dose-dependent manner. In contrast to CON veins, HC veins demonstrated an increase in sensitivity to NE and a contractile response to 5-HT (at 4 weeks only). HC veins did not relax in a dose-dependent manner in response to ACh. No changes in the morphology of HC veins were noted. HC produces changes in the structure and associated vasomotor abnormalities of vein grafts. Closely related functional changes also occur in contralateral veins. HC appears to induce intrinsic changes in smooth muscle cells which are linked to a greater proliferative and abnormal vasomotor capability. Clinically, applications of vigorous anti-HC regimens perioperatively may be beneficial in maintaining patency over the longer term.

Animals↗

PubMed1993

Reduction of experimental vein graft intimal hyperplasia by ketanserin.

Intimal hyperplasia is considered to be the result of smooth muscle cell proliferation. Experimental vein grafts (VG) in the rabbit develop intimal hyperplasia and a contractile response to serotonin (5-HT), mediated by a 5-HT2 receptor. 5-HT is known to stimulate smooth muscle cell proliferation in vitro and therefore may be linked to the development of intimal hyperplasia. This study examines the effect of a 5-HT2 antagonist, ketanserin (KT) on vein graft morphology and function at 14 and 28 days after grafting. Forty-three New Zealand White rabbits underwent common carotid interposition bypass grafting. Twenty-two were treated with KT (0.86 mg/kg/day po) 5 days prior to surgery and thereafter until harvest. The remaining 21 animals acted as controls. VG were harvested at 14 (VG14) and 28 (VG28) days for histology or vasoreactivity. Twenty-three VG were harvested by pressure fixation and the midportions of the grafts were examined by videomorphometry. Standard isometric tension studies in response to serotonin and norepinephrine (NE) were performed on the rings from the remaining 20 VG. Contralateral external jugular veins (CV) from both groups were studied to assess the functional toxicity of KT. There were no toxic effects to KT noted. KT therapy did not affect the functional activity of the CV at 14 or 28 days when compared to controls. When compared to controls, KT significantly reduced the intimal thickness (49 +/- 11 vs 113 +/- 24 microns; P = 0.04) and there was an increase in luminal area (16.89 +/- 2.13 vs 8.41 +/- 1.59 mm2; P < 0.02) in VG28 only.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Dilation of the internal mammary artery by external papaverine application to the pedicle--an improved method.

Spasm of the internal mammary artery (IMA) during coronary bypass grafting may cause inadequate graft flow and makes accurate placement of sutures difficult. In addition, IMAs with poor intraoperative flow rates are more likely to occlude. In this study three methods for spasm prevention were compared in 51 patients undergoing coronary bypass surgery. In group 1, IMA pedicles were covered with a sponge soaked with papaverine solution (0.8 mg/ml of papaverine in 0.9% saline) and left intact distally, thus allowing continuous blood flow until used for bypass. In group 2, the IMAs were divided and clamped distally and the pedicle tucked into a papaverine-soaked sponge. In group 3, the IMAs were also divided distally, clamped, and placed under the upper sternum submerged in papaverine solution (0.8 mg/ml) inside a surgical glove. Free flow from the IMA was higher in group 3 than in groups 1 and 2 (60 ml/min vs. 44 and 30, respectively, P < 0.03). Morphometric measurements disclosed a larger luminal area and less folding of the internal elastic lamina in group 3 compared with groups 1 and 2 (0.73 mm2 vs 0.33 and 0.37, respectively, P < 0.03). Submersion in papaverine solution thus provides better procurement of IMA grafts than storage of the pedicle in a papaverine-soaked sponge.

Adult↗