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Biomedical subjects

C Unterberg

Publications and source records attributed to C Unterberg.

At least 37 records · Page 2Linked to original sources

Reduced acute thrombus formation results in decreased neointimal proliferation after coronary angioplasty.

OBJECTIVES: We tested the hypothesis that reduced acute platelet deposition after angioplasty results in reduced late neointimal proliferation. BACKGROUND: Platelet-mediated mechanisms contribute to smooth muscle cell proliferation and migration. METHODS: Indium-111-labeled platelets were injected 16 h before coronary stent angioplasty in 10 Göttinger minipigs: group 1 (n = 5) = heparin (100-U/kg bolus) before angioplasty; group 2 (n = 5) = recombinant hirudin (CGP 39393, 1.0-mg/kg body weight bolus intravenously), followed by subcutaneous doses of 6 to 10 mg/kg every 8 h. Furthermore, stent angioplasty was performed in coronary arteries of 16 minipigs: group 3 (n = 5, nine stents) = 100 U/kg heparin only; group 4 (n = 5, 10 stents) = 1-mg/kg bolus hirudin before and 45 min after angioplasty; group 5 (n = 6, 11 stents) = hirudin (1-mg/kg intravenous bolus) before and 45 min after angioplasty, followed by 6 to 10 mg/kg subcutaneously every 8 h. RESULTS: In segments with deep arterial injury, the number of platelets/angioplasty segment in group 2 after 72 h (mean 21, range 9.7 to 39.7 x 10(6)) was significantly less than that in group 1 (mean 375, range 72 to 787 x 10(6)). Morphometric analysis after 4 weeks showed no difference between groups in degree of vessel wall injury. Mean (+/- SD) neointimal thickness was 0.70 +/- 0.06 mm in group 3 and was significantly reduced in both group 4 (0.46 +/- 0.11 mm) and group 5 (0.48 +/- 0.21 mm). CONCLUSIONS: The direct thrombin inhibitor hirudin significantly reduces platelet deposition up to 72 h after coronary stent angioplasty. A hirudin bolus alone as well as continued subcutaneous administration for 14 days substantially reduced neointimal proliferation compared with heparin 4 weeks after coronary stent angioplasty in minipigs.

Angioplasty, Balloon, Coronary↗

Expression of meta-vinculin in human coronary arteriosclerosis is related to the histological grade of plaque formation.

In the present study we demonstrate that the quantitative reduction of meta-vinculin expression parallels histological changes during the course of coronary arteriosclerosis. Immunofluorescence stainings of coronary arteries revealed that vinculin distribution resembled that of other smooth muscle-specific cytoskeletal proteins like alpha-actin, caldesmon or myosin light chain kinase in labeling smooth muscle cells brightly. Although close to arteriosclerotic plaques, the cellularity as measured by the density of nuclei was often not significantly altered. Cells of this location expressed markedly reduced amounts of vinculin, suggesting that they are smooth muscle cells of a synthetic phenotype. To determine the fractional meta-vinculin content in arteriosclerotic lesions, we performed densitometric scanning of immunoblots incubated with anti-vinculin monoclonal antibodies reacting with both meta-vinculin (150 kDa) and vinculin (130 kDa). In parallel, each tissue sample was evaluated histologically for the degree of arteriosclerotic alterations according to the morphometric atheroma score of Stratford et al. (n = 13). In type 1 lesions covering slight intimal thickening, meta-vinculin represented 36% (mean, range 35%-39%) of the total vinculin immunoreactivity. In type 2 lesions consisting of fibrous plaques of up to twice the original artery wall thickness, meta-vinculin accounted for 28% (mean, range 22%-35%) of the total vinculin content. Meta-vinculin was substantially reduced in type 3 lesions (mean 13%, range 8%-18%) which are characterized by extensive atheromatous plaques. Thus, the meta-vinculin/vinculin ratio differed significantly between early, intermediate and advanced phases of coronary arteriosclerotic plaque formation.

Aged↗

[Coronary angioplasty with controlled longitudinal dissection. Initial clinical results using a new cutting balloon].

A recently developed cutting balloon was used for coronary angioplasty in 21 patients (4 women, 17 men; mean age 57.6 [36-81] years) with coronary heart disease (angioplasty of the right coronary artery in 4, of the circumflex branch in 4, and of the anterior interventricular branch in 13 patients). The balloon contains 3-4 longitudinally arranged metal cutters to prevent uncontrolled vessel tears. An average stenosis reduction from 84 +/- 8.6% to 30 +/- 10.6% was achieved in ten patients. In the eleven others a second dilatation with a conventional balloon was necessary because of a residual stenosis of over 50% after the first dilatation with the cutting balloon. This reduced the original stenosis from 78.6 +/- 9.4% to 30.4 +/- 9.9%. Complete occlusion at the place of previous dilatation occurred in one patient 14 hours after the procedure, due to a dissection which required a stent implantation. These preliminary results suggest that the cutting balloon can achieve a stenosis reduction similar to that with a conventional balloon.

Adult↗

Cutting balloon coronary angioplasty--initial clinical experience.

The success of percutaneous transluminal coronary angioplasty is limited by acute occlusion and late restenosis. In 25 patients (20 men, 5 women, age range 36-81 years) coronary angioplasty was performed using a new cutting balloon into which 3-4 longitudinally orientated blades are incorporated so as to reduce the rate of severe dissections. In 12 patients stenoses were reduced from 83.9 +/- 7.8% to 28.4 +/- 10.7% (mean +/- SD) by the cutting balloon alone, using predilatation with a small conventional balloon in two cases. Thirteen other patients were additionally dilated with a conventional balloon because of a residual stenosis > 50% after cutting balloon angioplasty. Here the stenoses could be reduced from 78.1 +/- 8.7% to 29.1 +/- 11.3%. Six months follow-up angiography in 14 patients showed > 50% restenosis in two of seven patients dilated with a conventional balloon in addition to the cutting balloon, and in one of seven patients dilated with the cutting balloon alone but predilated with a small conventional balloon. These results show that coronary angioplasty by the new cutting balloon results in a stenosis reduction comparable with conventional balloons at a low complication rate. Available 6 months follow-up data show three restenoses in patients either pre- or postdilated by a conventional balloon and none in stand-alone cutting balloon cases.

Adult↗

Platelet and fibrin deposition on coronary stents in minipigs: effect of hirudin versus heparin.

OBJECTIVES: The present study was designed to test the hypothesis that the direct thrombin hirudin is more efficient than heparin in reducing thrombus formation after coronary stenting. BACKGROUND: Despite aggressive anticoagulation, subacute thrombosis of coronary stents is a major complication associated with these new devices. METHODS: In 19 minipigs indium-111-labeled thrombocytes and iodine-125-labeled fibrinogen were injected 14 to 19 h before coronary implantation of tantalum balloon-expandable stents. In group 1 (n = 6, seven stents), a bolus of heparin (100 U/kg body weight) was given before stenting. Group 2 (n = 6, 11 stents) received both dextran (500 ml) and heparin (a 100-U/kg bolus followed by a continuous infusion of 50 U/kg per h). In group 3 (n = 7, 13 stents), hirudin (recombinant desulphatohirudin HV 1 [CGP 39393] [1 mg/kg]) was given before stent implantation, followed by an infusion of 1 mg/kg per h. All animals were pretreated with aspirin (250 mg intravenously). RESULTS: Activated partial thromboplastin time was prolonged to > 1.8 times control values in groups 2 and 3. Histologic examination after perfusion fixation 12 h after stenting showed a variable extent of thrombus on all stents. Medial tear was observed in three stents in group 1, six stents in group 2 and six stents in group 3. The number of platelets on all stents averaged 116.2 (range 22 to 522) x 10(6) in group 1, 64.3 (range 11 to 169) x 10(6) in group 2 and 19.7 (range 9 to 38) x 10(6) in group 3 (p < 0.05 vs. group 1 and vs. group 2). The increase in platelet deposition, associated with medial tear in all groups, was lowest in the hirudin group. Similarly, fibrin deposition was lowest on stents in hirudin-treated animals. CONCLUSIONS: Recombinant hirudin significantly reduces platelet and fibrin deposition on coronary stents compared with the reduction achieved with combined heparin, dextran and aspirin.

Angioplasty, Balloon, Coronary↗

Restenosis after excimer laser angioplasty of coronary stenoses and chronic total occlusions.

In an open clinical study, a xenon-chloride excimer laser was used for angioplasty of coronary stenoses (n = 48) and chronic total occlusions (n = 56) in 104 patients. Multifiber catheters (4.0F to 5.5F) transmitted 37 to 120 mjoules/mm2 of fiber surface. Excimer laser angioplasty was successful in 43 patients with a stenosis (89%), followed by percutaneous transluminal coronary angioplasty in 21 patients (49%) to reduce the stenosis to less than 50% luminal narrowing. In 39 patients (70%) with a chronic occlusion (age 1 to 14 months), recanalization by means of excimer laser angioplasty was successful, with subsequent percutaneous transluminal coronary angioplasty performed in 23 patients. Major complications included one perforation, one acute occlusion, and two severe dissections. Six-month angiographic follow-up examinations after successful angioplasty were completed in 40 patients (98%) with stenoses and 34 (94%) with occlusions. Restenosis (greater than 20% decrease in luminal diameter) occurred in 13 patients (33%) with stenoses and in 16 patients (47%) after angioplasty of a chronic occlusion. These long-term results indicate that restenosis after excimer laser angioplasty of coronary stenoses and chronic total occlusions is similar to reported results of conventional balloon angioplasty.

Angioplasty, Balloon↗

Low-molecular-weight heparin reduces neointimal proliferation after coronary stent implantation in hypercholesterolemic minipigs.

BACKGROUND: Intracoronary stents have been suggested as a method of reducing the restenosis rate after balloon angioplasty. Proliferation of vascular smooth muscle cells is a major contributing factor to the restenosis process. Heparin and some of its derivatives have been shown to inhibit smooth muscle cell proliferation. We investigated the effect of low-molecular-weight heparin on the proliferative response after implantation of a balloon-expandable tantalum stent in previously deendothelialized coronary artery segments of hypercholesterolemic minipigs. METHODS AND RESULTS: Minipigs were fed a diet containing 2% cholesterol, starting 1 month before balloon denudation of the endothelium in a coronary artery. One month later, a stent was implanted at this site. Animals were killed after 4 weeks (group 1, n = 6) or 3 months (group 2, n = 6). Animals in group 3 (n = 6), also followed for 4 weeks after stenting, received subcutaneous low-molecular-weight heparin at a dose of 200-300 units/kg anti-factor Xa activity per day in addition to the chronic acetylsalicylic acid (100 mg/day) also administered to groups 1 and 2. Eighteen of 22 animals survived to the end of the study. Angiography revealed patent stents in all surviving animals. In group 1, histological analysis showed extensive neointimal proliferation around stent struts. Maximal neointimal thickness seen in group 1 averaged 0.93 +/- 0.11 mm, was lower after 3 months (0.8 +/- 0.14 mm) in group 2, but was significantly reduced (0.44 +/- 0.18 mm, p less than 0.01) in group 3. CONCLUSIONS: These data show a significant reduction of the neointimal proliferative response to coronary stent implantation by low-molecular-weight heparin.

Animals↗

Coronary angioplasty in patients with previous coronary artery bypass grafting.

Between 1982 and 1990, in 134 patients with prior coronary artery bypass grafting and recurrent angina, repeat coronary angiography and balloon angioplasty of stenoses in grafts or native arteries were attempted. Mean age of grafts was 45.6 months, range three days to twelve years. At the time of angioplasty, 6 patients had one-vessel-disease, 33 had two-vessel-disease, and 95 had three-vessel-disease. A total of 182 lesions were dilated: 55 venous grafts, 3 internal mammary artery grafts, and 124 native vessels. Forty-nine of 55 (89%) venous grafts could be successfully dilated, and in 3 internal mammary artery grafts, a stenosis reduction greater than 50% was achieved. In 65 of 88 (74%) grafted native arteries, dilation success was achieved. Twenty-seven of 36 (75%) patients with prior bypass surgery to other arteries had successful angioplasty of nongrafted native arteries. Three patients underwent emergency bypass surgery after dissection and acute occlusion: one of them died in cardiogenic shock secondary to acute myocardial infarction. The angiographic success rate in grafts was slightly higher than in native arteries (90% vs 74%). These data indicate that percutaneous transluminal coronary angioplasty in patients after bypass surgery is possible at a low risk (3%) and constitutes an effective therapy in symptomatic patients.

Aged↗

Initial clinical results with the Wiktor stent: a new balloon-expandable coronary stent.

The Wiktor stent, a new coronary balloon-expandable tantalum stent, was implanted in 17 patients for other wise nonmanageable occlusion after balloon angioplasty (n = 11) and for recurrent restenosis (n = 6). Stents of 3.0 to 4.0 mm were implanted (right coronary artery: n = 10, left anterior descending artery: n = 4, left circumflex artery: n = 2, venous graft: n = 1). All patients were fully anticoagulated initially with heparin followed by coumadin for 3 months and were treated with acetylsalicylic acid indefinitely. Due to its good radiopacity, the device could be placed easily without complications. Early occlusion occurred in one patient after 8 h probably due to friable atheromatous material prolapsing between the meshes of the stent. Late occlusion occurred in another patient who was admitted in cardiogenic shock after pre-hospital reanimation and was stented after occlusive disection following balloon angioplasty of an occluded right coronary artery. In this patient with severe hypoxic brain damage, reocclusion and reinfarction to which the patient finally succumbed occurred following cessation of anticoagulation. Histology demonstrated occlusive thrombosis without evidence of a neointimal covering of the stent. Another thrombotic occlusion due to inadvertent omission of anticoagulation occurred in another patient two weeks after stenting. Control angiography after 6 months in 12 patients revealed restenosis in two patients (50% and 80%). The patient with 80% restenosis of the right coronary artery and pathologic results during stress testing underwent surgical revascularization. The other patient with a 50% restenosis of the right coronary artery was managed medically as he was asymptomatic and without evidence of ischemia during stress testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

Excimer laser angioplasty in coronary artery disease.

The results of coronary excimer laser angioplasty were evaluated in 70 patients. Forty-five patients had laser angioplasty of coronary stenoses. Twenty-five patients in a total of 35 attempts had wire-guided laser recanalization of chronic coronary occlusions, resulting in a success rate of 71%. Immediate results in both groups demonstrated the efficacy of this technique without serious side-effects. Stenoses were reduced from 90 +/- 5% to 48 +/- 18% diameter reduction (mean +/- standard deviation) by excimer laser angioplasty. Residual stenosis in recanalized vessels after laser angioplasty was 52 +/- 19%. In slightly more than half of the patients with a residual stenosis greater than 50% after excimer laser angioplasty, subsequent balloon angioplasty was performed for further stenosis reduction. While satisfactory immediate results were achieved by excimer laser angioplasty intermediate follow-up revealed a restenosis rate in the same range as with balloon angioplasty.

Aged↗

Recanalization of chronic total coronary arterial occlusions by percutaneous excimer-laser and laser-assisted angioplasty.

A low primary success and high restenosis rate after recanalization of chronic total occlusions by conventional coronary angioplasty have encouraged the application of new interventional techniques like excimer-laser angioplasty. In 39 patients with a coronary occlusion for 1 to 12 months, recanalization was attempted by laser angioplasty through a multifiber-catheter coupled to a pulsed XeCl excimer laser. After successful passage of the occlusion by a standard guidewire in 27 patients (69%), the laser catheter was advanced over the central guidewire and crossed the occlusion in 25 patients (64%). In 2 patients with unsuccessful passage of the laser catheter, the subsequent attempt with a low profile balloon catheter also failed. In 19 of the 25 patients with successful laser recanalization, the residual stenosis exceeded 50% and was therefore followed by additional balloon angioplasty. The average residual stenosis after laser was 61 +/- 17% of the vessel diameter, and after balloon angioplasty 28 +/- 9% (n = 19), whereas after laser angioplasty alone it was 38 +/- 5% (n = 6). No complications associated with the laser application were observed. Angiographic control after 24 hours showed a reocclusion of 2 (8%) recanalized vessels. In this pilot study, laser angioplasty proved to be a safe and feasible method for the treatment of chronic total coronary occlusions. Because it was necessary to guide the catheter by a central wire, the primary success was limited by a successful passage of the wire of the occlusion. The rate of stand-alone laser angioplasty has to be increased by future improvements of the technique to enable a comparative evaluation of this method with conventional angioplasty.

Angioplasty, Laser↗

Cardiac fatty acid-binding proteins. Isolation and characterization of the mitochondrial fatty acid-binding protein and its structural relationship with the cytosolic isoforms.

In the course of our studies on the structural diversity of the isoforms of cardiac fatty acid-binding proteins (cFABPs), a cardiac-type FABP from the matrix of bovine heart mitochondria was purified to homogeneity and obtained as a single 15-kDa protein with an isoelectric point of 4.9. The primary structures of this protein and of the two isoforms isolated from the cytosol (pI4.9-cFABP and pI 5.1-cFABP) were investigated by means of plasma desorption mass spectrometry and sequencing of peptides. All three proteins are amino-terminally blocked with an acetyl group and shown to be colinear with the sequence deduced from a cDNA clone for bovine heart fatty acid-binding protein (Billich, S., Wissel, T., Kratzin, H., Hahn, U., Hagenhoff, B., Lezius, A. G., and Spener, F. (1988) Eur. J. Biochem. 175, 549-556) except for the residue at position 98. This residue is demonstrated to be the molecular origin of bovine cFABP isoforms since pI 5.1-cFABP contains Asn98 in accordance with the sequence derived from the cDNA, whereas in pI 4.9-cFABP, this position is occupied by Asp98. Moreover, mitochondrial FABP is identical to pI 4.9-cFABP. Molecular masses of pI 4.9-cFABP (14,679 +/- 10 Da) and pI 5.1-cFABP (14,678 +/- 20 Da) determined by plasma desorption mass spectrometry coincide with that calculated from the cDNA (14,673 Da). Hence, residues linked to these proteins by posttranslational modification are not present, and the Asn-Asp exchange is the sole origin of heterogeneity of mitochondrial and cytosolic fatty acid-binding proteins from bovine heart.

Amino Acid Sequence↗

Severe granulomatous giant cell myocarditis in Wegener's granulomatosis.

A 28-year-old male patient suffering from Wegener's granulomatosis died suddenly with signs of cardiac failure after clinical symptoms had basically subsided under chemotherapy. Autopsy revealed pulmonary granulomata, necrotizing vasculitis of the lungs and kidneys, focal and segmental necrotizing glomerulonephritis, and diffuse granulomatous and necrotizing giant cell myocarditis. Histological confirmation of inflammation of the heart in Wegener's disease has rarely been reported. Although cardiac involvement in Wegener's granulomatosis sometimes is suspected, it is usually thought to have no major impact on the course of the disease. By its dramatic clinical and morphologic presentation this case illustrates that the heart, in addition to the lungs and kidneys, may determine the outcome of the idiopathic granulomatous vasculitis of Wegener.

Adult↗

[Acute effects of the angiotensin converting enzyme inhibitor ramipril in patients with coronary heart disease].

We investigated the acute effect of the new long-acting ACE-inhibitor ramipril on angina-limited exercise tolerance and exercise-induced ST-depression in 18 normotensive patients with angiographically confirmed coronary artery disease in a double-blind, placebo-controlled study. Patients underwent a repeat exercise ECG 24 hours following either 5 mg ramipril p.o. or placebo. Plasma-ACE activity (nmol/min x ml) in the ramipril-group (n = 8) was significantly reduced 24 hours after 5 mg ramipril compared to placebo (n = 10): 14.0 +/- 2.0 vs 87.2 +/- 13.5, p less than 0.001. Exercise-induced ST-segment depression was not different before and after ramipril or placebo. Heart rate at rest and during angina-limited exercise was not different between the first exercise-ECG and that after ramipril or placebo, nor between the groups. Systolic arterial pressure (mmHg) was slightly, but insignificantly, lower after than before ramipril at rest (113.8 +/- 5 vs 125 +/- 6.8) and at maximal exercise, 1.5 watt/kg (150 +/- 9.4 vs 158.3 +/- 13.3). In the placebo group, blood pressure at rest and during exercise was not different before and after placebo: 126 +/- 4.7 vs 125.5 +/- 7.5 and 157.5 +/- 3.8 vs 158 +/- 3.6. Rate-pressure-product (mmHg/min x 1000) at rest prior to (8.42 +/- 0.83 and 8.95 +/- 0.51) and after ramipril or placebo (8.00 +/- 0.94 and 8.93 +/- 0.71) showed no significant difference. Similarly, rate-pressure-product at maximal exercise was equal among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Malignant restenosis after primary successful excimer laser coronary angioplasty.

In a series of 20 coronary excimer laser angioplasties, two patients presented with a peculiar type of malignant restenosis 6 and 8 weeks after a successful laser angioplasty procedure. One patient had a successful recanalization of an occluded left anterior descending (LAD) coronary artery and the second patient had a successful angioplasty of a subtotal proximal stenosis of the left anterior descending coronary artery. After the procedure, no ischemia could be demonstrated by exercise ECG and thallium scintigraphy. Both patients were free of angina until the sudden development of nocturnal angina several hours before reangiography, which showed subtotal restenosis in both cases. One patient had a mammaria graft on the LAD and the second patient underwent a successful balloon angioplasty. This uncommon sudden and malignant development of restenosis seems to be related to the excimer laser angioplasty procedure and warrants some caution with the indiscriminative use of this new angioplasty procedure.

Aged↗

Alterations of the mitochondrial respiratory chain in human dilated cardiomyopathy.

The defects underlying the impairment of systolic pump function in human dilated cardiomyopathy (DCM) are not known. We isolated mitochondrial particles from 10 hearts of transplant recipients with DCM and from nine normal hearts not used for transplantation. Yield was similar in both groups (2.77 vs 2.81 mg mitochondrial protein per gram heart). Cytochrome content (difference spectrophotometry) was found reduced in DCM mitochondria, e.g. cytochrome c was 0.295 +/- 0.06 in the DCM group and 0.371 +/- 0.04 mumol g-1 in the control group (P less than 0.05). Enzymatic activity of the cytochrome-containing complexes III (3.77 +/- 0.82 vs 4.95 +/- 1.15 mumol min-1.mg-1) and IV (2.63 +/- 0.96 vs 3.65 +/- 0.6 mumol min-1.mg-1) of the respiratory chain was reduced in the DCM group (P less than 0.05). Complex IV, the cytochrome c oxidase, in the DCM group showed impaired activity also in whole heart homogenates (0.173 +/- 0.04 vs 0.258 +/- 0.8 mumol min-1.mg-1). Subunit composition of the cytochrome c oxidase on sodium dodecyl sulphate-gel electrophoresis did not differ between DCM and normal hearts. Activity of complexes II and V of the respiratory chain, not containing cytochromes, was unchanged in DCM mitochondria compared with the control group. The present data show a decrease in cytochrome content and in cytochrome-dependent enzyme activity in human dilated cardiomyopathy. Further studies are necessary to clarify whether these findings are specific for dilated cardiomyopathy or whether they are epiphenomena of failing hearts.

Apyrase↗

[Acute hemodynamic effects of the vasodilator beta blocker carvedilol in heart failure].

The beta-blocker carvedilol has been shown to induce vasodilation in patients with coronary artery disease. In a double-blind, randomized, placebo-controlled cross-over study, we looked for the acute vasodilating effect after i.v. administration in patients with heart failure. In 10 patients with coronary artery disease and six patients with dilated cardiomyopathy, all with an ejection fraction lower than 40%, the rate-pressure-product during supine ergometry and Swan-Ganz-catheterization rose to a significantly smaller extent after 5 mg carvedilol i.v. compared to placebo. This was mainly due to a lower heart rate at rest and during exercise, while blood pressure was not changed compared to placebo. Calculated total peripheral resistance during exercise after carvedilol was higher--significantly so in the CAD-group--than after placebo. These results show that in patients with heart failure, an acute vasodilating effect of i.v. carvedilol is not detectable.

Adrenergic beta-Antagonists↗