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Background: Oxidative stress and endothelial dysfunction have been introduced as a unifying pathological mechanism for early atherosclerotic disease. They are caused by a variety of stimuli including cigarette smoking (environmental) and type 2 diabetes (disease factor). However, the role of hyperinsulinemia, a marker of insulin resistance, as a risk factor for atherosclerosis remains to be clarified., Study Objectives: To study the relationship of smoking, hyperinsulinaemia and biochemical markers of oxidative stress and endothelial dysfunction, in patients with coronary artery disease., Design: Case-control study of 5-year survivor status in smokers, former smokers and nonsmokers with angiographically documented stable coronary artery disease classified by self-reporting of smoking status together with plasma cotinine measurements., Setting: Cardiology and cardiac surgery unit of a tertiary care referral centre., Patients and Methods: Plasma levels of vitamins C, E and selenium, and the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were assessed in 214 patients at baseline together with the glucose and insulin response to an oral glucose challenge. Sixty known or newly diagnosed type 2 diabetic patients (28%) were identified and excluded from further analysis., Results: E-selectin and ICAM-1, serving as markers of endothelial dysfunction, significantly correlated with hyperinsulinaemia (p < 0.05). Circulating immunoreactive insulin was elevated in active smokers and former smokers as compared to non-smokers after an oral glucose load (p < 0.05 for the area under the insulin time curve), despite a similar glucose response. Smoking was associated with a decrease in antioxidant vitamins C (p = 0.02) and E (p = 0.03), and an increase of E-selectin (p < 0.05) and ICAM-1 (p < 0.001). Low baseline ICAM-1 and high vitamin C levels emerged as the most significant multivariate predictors of 5-year survival (p < 0.001)., Conclusions: Hyperinsulinaemia in smokers is linked with markers of endothelial dysfunction. Impaired vascular reactivity can thus be a new possible mechanism linking insulin resistance and smoking.

The early 4 French (Fr), pre-formed, Judkins coronary catheters had unsatisfactory maneuverability due to reduced torque stability. Technical innovations have led to improved 4 Fr catheters. This prospective study evaluates the safety and feasibility of the 4 Fr Quick Care Infinity catheter (Cordis, Miami, Florida). Within a series of 2,366 patients investigated for suspected coronary artery disease, 302 were selected for outpatient treatment according to the guidelines for outpatient catheterization. Fluoroscopy time was 2.8 +/- 2.5 minutes. It was not necessary to change to larger catheters in any patient. After sheath removal, hemostasis was achieved within 14 +/- 8 minutes. Strict bed rest lasted 181 +/- 65 minutes; patients were discharged 303 +/- 76 minutes after arterial puncture. Sixteen of the 302 patients (5.3%; 95% confidence interval (CI): 3.1-7.9%) changed to inpatient treatment for reasons unrelated to the arterial access. Eight patients (2.6%; CI: 1.1-5.1%) required one night of hospitalization for control of hematoma. The following morning, vessel murmur, pain, and large hematoma (more than 10 cm diameter) occurred in 1 (0.3%), 6 (2.0%), and 6 (2.0%) patients, respectively. This necessitated hospital admission in 2 patients (0.7%; CI: 0.0-2.3%) for up to 2 days. Major entry site complications requiring blood transfusion or surgery did not occur (CI: 0.0-0.3%). It was concluded that outpatient catheterization for coronary artery disease using the new 4 French catheters is feasible and can be rapidly and safely performed in a selected patient population.

Objective: It was the goal of this study to compare endothelium-dependent and endothelium-independent flow reserve in vascular regions supplied by the left internal mammary artery before and after bypass graft surgery., Methods: The native internal mammary artery in situ was investigated in 13 patients (age 61.8 +/- 8.0 years) with angiographically proven coronary artery disease. The internal mammary artery after bypass grafting was investigated in ten patients (age 60.8 +/- 7.3 years) 3.5 +/- 2.8 years after the operation. Flow reserve was evaluated endothelium-dependent with acetylcholine (ACh 25 and 50 microg i.c.) and endothelium-independent with nitroglycerin (NTG 0.3 mg i.c.) followed by papaverin (10 mg i.c.). Flow indices were calculated from intraluminal Doppler blood flow velocity measurements and the vascular cross-sectional area as determined by quantitative angiography. An index for vascular resistance was defined as the ratio of pressure gradient and resting or peak flow., Results: After endothelium-dependent stimulation with acetylcholine 25 microg (50 microg), flow in the internal mammary increased by 352.3 +/- 152% (412 +/- 145%) before surgery, whereas it increased only by 213 +/- 134% (193 +/- 120%) after surgery (P < 0.05). Endothelium independent stimulation with papaverin resulted in a flow increase of 391 +/- 234% before surgery vs. 315 +/- 135% after surgery (n.s.). The resistance index decreased after endothelium-dependent stimulation with acetylcholine 25 microg(50 microg) to 35 +/- 16.8% (28 +/- 8.9%) before surgery, whereas it decreased only to 59 +/- 26% (72 +/- 43%) after surgery (P < 0.05). Endothelium independent stimulation with papaverin resulted in a decrease of the vascular resistance index to 31 +/- 14% before surgery vs. 32 +/- 14% after surgery (n.s.)., Conclusion: Vascular regions supplied by the internal mammary artery as a graft demonstrate a significantly reduced endothelium-dependent flow reserve but a preserved endothelium-independent flow reserve as compared to vascular regions supplied by the native internal mammary artery. The selective decrease in endothelium-dependent flow reserve may be due to microvascular changes in the myocardial region supplied by the internal mammary artery after bypass grafting.

In a 22-year-old woman with recent onset of left-sided chest pain and exertional dyspnea, echocardiography revealed obstruction of a St. Jude Medical bileaflet prosthetic valve (size 23 mm) in the pulmonary position. Oral anticoagulation had been replaced for the previous 7 years by aspirin as the sole antithrombotic treatment. The valve had been inserted 16 years ago for pulmonary atresia. Valve function was restored by systemic application of 9 million units of urokinase.

Aim of this study was to evaluate right ventricular performance in patients with mitral stenosis and its modification by balloon valvuloplasty. Right ventricular volumes of 24 patients with postrheumatic mitral stenosis were determined by thermodilution 1 or 2 days before and 1 or 2 days after valvuloplasty. Right ventricular ejection fraction at rest was 43 (36-47)% (median and interquartile range). Right ventricular end-diastolic volume was 100 (86-119) ml/m2. Supine bicycle exercise (50 Watt) reduced right ventricular ejection fraction to 30 (29-37)% (P < 0.0001) and increased right ventricular end-diastolic volume to 124 (112-141) ml/m2 (P < 0.0001). At rest, right ventricular ejection fraction correlated inversely with pulmonary vascular resistance (r = -0.64, P < 0.0001), while no significant correlation with mitral valve area was found. Valvuloplasty increased right ventricular ejection fraction at rest to 48 (44-50)% (P < 0.005), and during exercise to 42 (38-45)% (P < 0.0001). This improvement of right ventricular ejection fraction correlated inversely with the value of this parameter before valvuloplasty (r = -0.88, P < 0.0001) and with the gain in stroke volume (r = 0.57, P < 0.01). The right ventricular function curve, disturbed before commissurotomy, was reestablished by the procedure. In conclusion, at the here investigated stage of mitral stenosis right ventricular function is reversibly impaired. This is predominantly caused by the hemodynamic consequences of the valvular defect and not by an impairment of right ventricular myocardial function.

Ca(2+)-channel blockers of the verapamil type have been reported to exert a beneficial effect on clinical symptoms and survival rates in hypertrophic cardiomyopathy. The effects of verapamil have been attributed predominantly to an improved diastolic filling. It is unknown whether an effect on diastolic filling persists in these patients after long-term treatment. Fourteen patients (12 men, 2 women, median age fifty-one [thirty-two to fifty-five] years) with hypertrophic cardiomyopathy were included in the study. Patients had been treated with verapamil 240-480 mg/d or gallopamil 150-200 mg/d for fourteen (seven to seventeen) years. The effect of a withdrawal of Ca(2+)-channel blockers on parameters of left ventricular diastolic function was evaluated at rest and during exercise in patients with hypertrophic cardiomyopathy after long-term therapy. Investigations were performed at rest and during supine ergometric exercise during ongoing Ca(2+)-channel blocking therapy and after five (four to nine) days' withdrawal (control). Pulsed Doppler echocardiography was used to record diastolic mitral flow profiles from an apical four-chamber view. Withdrawal of Ca(2+)-channel blockers of the phenylalkylamine type after long-term treatment of hypertrophic cardiomyopathy resulted in a significant reduction of early diastolic inflow velocity at rest and during exercise. In conclusion, these results indicate a persistent improvement of early diastolic filling by Ca(2+)-channel blockers even after long-term treatment.

Unlabelled: Forty patients (30 men, 10 women) with severe congestive heart failure NYHA III (n = 30) and IV (n = 10) due to coronary heart disease (n = 19) or dilative cardiomyopathy (n = 21) were enrolled in this study. Mean age was 57 years. Eight patients each received 0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg piroximone intravenously or placebo (saline). Measurements were performed before and up to 4 h after drug administration using a Swan-Ganz right-heart thermodilution catheter., Results: All changes stated were significant (p < 0.05). Pulmonary capillary wedge pressure was lowered by max. 27% (0.25 mg/kg) to 52% (2.0 mg/kg) 30 min after drug injection. Significant effects were seen for 60 (0.25 mg/kg) to 120 min (2.0 mg/kg). Mean pulmonary artery pressure decreased by max. 8% to 24% after 30 min. Effects lasted for 30 to 60 min. Cardiac index increased by max. 26% to 52% after 30 min. Significant changes occurred up to 4 h after 2.0 mg/kg. Systemic vascular resistance fell by max. 16% to 34%. Effect duration was 1 h (0.5 mg/kg up to 4 h) (2.0 mg/kg). Minor changes of arterial blood pressure (minus 7% after 0.5 mg/kg) and heart rate (minus 14% after 2.0 mg/kg) were seen., Conclusion: Small doses of piroximone i.v. increase cardiac output by about 20% while preload and afterload decrease by about 20%. For most cases no doses higher than 0.5 mg/kg will be needed for the treatment of severe congestive heart failure.

Between January 1979 and October 1991, percutaneous transluminal angioplasty of stenosed or occluded coronary bypass grafts was attempted 180 times in 146 patients (180 lesions in 157 bypass grafts); 6/157 grafts were internal mammary grafts. The procedure was successful in 129/157 grafts (82%) and in 151/180 lesions (84%). Failures occurred almost exclusively in recanalization attempts. Cardiac complications occurred in 4/146 patients (2.7%). Three patients developed an acute myocardial infarction, another patient died after acute occlusion of a native vessel dilated during the same procedure. In successful attempts the severity of stenosis was reduced from 87 +/- 10% to 33 +/- 15%. 113/129 successfully dilated grafts had at least one (mean 2.7) control angiogram. 54/113 (48%) showed recurrence after a mean follow up of 6 months. An additional 15 grafts showed late restenosis in a second control angiogram (mean follow-up 23 months). The total restenosis rate was 61%. Restenoses were dilated again one to six times (mean 1.9) with comparable success and recurrence rate. Two patients died during the sixth angioplasty. Finally, 32/129 (25%) grafts were occluded or presumably occluded, and 97/129 (75%) were angiographically confirmed open without restenosis. Thus, angioplasty of bypass grafts is an alternative to a repeat revascularization surgery. The acute results are comparable to the results of angioplasty in native coronary arteries. The restenosis rate is high. One has to be aware of late restenosis. Restenosis can be dilated repeatedly with a comparable success rate and with no significant increase in restenosis rate.

Unlabelled: Postrheumatic mitral stenosis might cause impairment of right ventricular (RV) function due to both an increase in RV afterload and rheumatic myocardial disease. Therefore, we investigated in 19 patients with postrheumatic mitral stenosis and sinus rhythm right ventricular volumes and hemodynamics by a computerized thermodilution catheter during rest and supine bicycle exercise. In 14 patients the investigation was repeated within 2 days after balloon mitral valvuloplasty. Resting RV ejection fraction was decreased (43 (15-53)%, median (range)) and correlated significantly with RV end-systolic volume index (r = -0.90), stroke volume index (r = 0.77), RV end-diastolic volume index (r = -0.76), heart rate (r = -0.69), pulmonary artery resistance (r = -0.69), and mean pulmonary artery pressure (r = -0.68). RV end-diastolic volume index was 107 (81-200) ml/m2. Exercise induced a decrease of RV ejection fraction to 36 (13-48)% at 50 Watt (p < 0.001), while it increased RV end-diastolic volume index to 131 (78-231) ml/m2 (p < 0.001). Balloon mitral valvuloplasty improved RV ejection fraction at rest from 41 (15-47)% to 48 (39-55)% (p < 0.005) and from 30 (13-46)% to 43 (27-56)% during exercise (p < 0.005). The increase of RV ejection fraction after valvuloplasty was caused by an increase in stroke volume, but not by a reduction in RV end-diastolic volume., Conclusion: Depending on the increased RV afterload, RV function is markedly depressed in mitral stenosis. An immediate and almost complete improvement of RV function occurs with the reduction of RV afterload after balloon mitral valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

The unprotected left main stenosis still represents one of the contraindications of PTCA; recently developed concepts using percutaneous bypass techniques have not changed this fact so far. However, following bypass grafting the procedure can be done with low risk and may improve prognosis in case of later bypass occlusion. This study should clarify whether a higher rate of bypass occlusion is caused by postsurgical left main PTCA. From October 1981 to January 1991 a left main stenosis was dilated in 41 patients, 2 weeks to 12 years (mean 3.5 years) after bypass grafting. To date, 17/65 venous bypass grafts were already occluded, and 72.4% of the patients suffered from typical angina. In 34/41 patients (82.9%) PTCA was successful, severe complications (death, emergency surgery or myocardial infarction) did not occur and clinical improvement was achieved in 80% of symptomatic patients. Four months later, 26/34 patients (76.5%) had angiographic follow-up. Fifteen restenoses were found and a second PTCA was performed in 9/15. None of the venous bypass grafts, open at the time of the first PTCA, was occluded at follow-up. In one case PTCA of the left main stenosis turned out to be life-saving 7 years later because an occlusion of RCA- and LCX-bypasses occurred and the LAD graft showed a subtotal thrombosis. It is concluded that PTCA of left main stenosis after bypass grafting is a safe procedure and does not lead to a higher rate of venous bypass occlusions. A prognostic indication seems to be justified.

In chronic coronary occlusions the rate of successful reopening seems to be improved with the help of new techniques; the chance of success can be judged by the age of occlusion. Frequently this age cannot be fixed exactly. The purpose of the study was therefore to find out, whether the chance of reopening can be judged by morphology. 60 patients in whom the occlusions could not be passed with a conventional wire were treated with the ROTACS system. Cine angios were reviewed carefully, morphological details in at least two projections were evaluated in graphic representations and correlated with the acute success rate and the estimated age of occlusion. Morphological parameters associated with a higher rate of success (type A) were: 1) a clearcut proximal stump with 2) no sidebranches at the site of occlusion, 3) no bridging collaterals and 4) only a slight filling of the distal vessel. Parameters with a low success rate (type B) were: 1) no proximal stump, 2) sidebranches at the site of occlusion, 3) bridging collaterals and 4) a very good distal filling. 48/60 (80%) of occlusions could be classified in type A or type B. The success rate was 17/21 (81%) (type A) versus 5/27 (18.5%) (type B) (p < 0.0002). The estimated age of type B occlusions was significantly higher than in type A: median 8 versus median 4 months (p < 0.002). It is concluded that the rate of success in reopening chronic coronary occlusions can be judged in the majority of patients using morphological parameters.

In the present paper, the contribution of TM 2D and Doppler echocardiography to the non-invasive diagnostic evaluation of hypertrophic cardiomyopathies is discussed. The selective use of various echocardiographic possibilities for the representation (visualization) of typical morphological and functional changes in hypertrophic myocardial diseases is described.

Percutaneously introduced absorbable purified bovine collagen was used to plug the hole at the site of femoral arterial puncture in 50 patients (42 men, 8 women; median age 58 [22-75] after percutaneous coronary angiography (n = 32; heparin dosage 100 IU/kg) or transluminal coronary balloon dilatation (n = 18; heparin dosage 200 U/kg). Local bleeding ceased after compression of 4 min in 48 of the 50 patients. A pressure bandage was needed additionally in the other two. Bed-rest lasted for 1-24 (median 19) hours. A haematoma of more than 6 cm diameter developed in five patients, but required neither transfusion nor surgical intervention. 39 of the 50 patients were re-examined after a median of 39 days: all of them had had a small pain-free swelling for 2-6 weeks over the puncture site. One patient developed a deep-vein thrombosis one week after the procedure, in another fever occurred after the same period, lasting for two days. These early findings are encouraging. The method may significantly shorten the time of arterial compression and bed-rest, as well as reduce the risk of a large haematoma after arterial punctures.

Synthesis of 7-O-(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)-epsilon-(i so)rhodomycinones 16 and 17, and their 3'-morpholino derivatives are described. Glycosylation (trimethylsilyl triflate, 10:1 dichloro-methane-acetone, -35 degrees) of 1-O-tert-butyldimethylsilyl-2,3-6-trideoxy-4-O-p-nitrobenzoyl-3-trifl uoroacetamido-beta-L-lyxo-hexopyranose (4) with epsilon-rhodomycinone (epsilon-RMN, 5) or epsilon-isorhodomycinone (epsilon-isoRMN, 6) afforded 7-O-alpha-glycosyl-epsilon-RMN (9) and -epsilon-isoRMN (12) in high yield. The glycosyl donors 2,3,6-trideoxy-4-O-p-nitrobenzoyl-3-trifluoroacetamido-L-lyxo++ +-hexopyrano se (2) or its 1-O-trimethylsilylated alpha-anomer 3 were less suitable for the glycosylation of these aglycons. Sapinification of 9 and 12 provided 16 and 17, respectively, which reacted with various 2,2'-oxydiacetaldehydes under conditions of reductive alkylation to give 3'-morpholinyl-epsilon-(iso)rhodomycins.

Unlabelled: The acute effects of enoximone (E) and captopril (C) were compared in a single-blind, randomized, cross-over trial in 10 patients (P) (nine with dilative cardiomyopathy, one with coronary heart disease) with heart failure (NYHA Class III: 6P and Class IV:4P). Cardiac index (Cl, 1/min.nm(-2), mean pulmonary artery pressure (PAM, mmHg), and pulmonary capillary wedge pressure (PC, mmHg) were measured at baseline and 15, 30, and 60 min after 0.1 mg/kg C and 0.75 mg/kg E, respectively, followed by measurements at 15, 30, 60, 180, and 300 min after 0.2 mg/kg C and 1,5 mg/kg E, respectively., Results: Cl was unchanged 60 min after 0.1 mg/kg C, increased 60 min after 0.2 mg/kg C by 7.7% from 2.1 +/- 0.5 to 2.4 +/- 0.5 (p = 0,001), and was unchanged after 5 h. Cl increased 60 min after 0.75 mg/kg E by 32.5% from 2.1 +/- 0.5 to 2.9 +/- 0.4 (p = 0.001), 60 min after 1,5 mg/kg E by 59% to 3.3 +/- 0.6 (p = 0,001), and after 5 h by 19% to 2.5 +/- 0.4 (p = 0.01). PAM was unchanged 60 min after 0.1 mg/kg C, decreased 60 min after 0.2 mg/kg C by 10% from 35.7 +/- 11 to 31.7 +/- 10, and was unchanged after 5 h. PAM decreased 60 min after 0.75 mg/kg E by 13% from 35 +/- 9 to 31 +/- 10 (p = 0.01), 60 min after 1.5 mg/kg E by 19% from 35 +/- 9 to 27 +/- 9 (p = 0.001), and was unchanged after 5 h. PC decreased 60 min after 0.1 mg/kg C by 23% from 24 +/- 8 to 19 +/- 9 (p = 0.05) and was unchanged 60 min und 5 h after 0.2 mg/kg C. PC decreased 60 min after 0.75 mg/kg E by 35% from 25 +/- 6 to 17 +/- 8 (p = 0,01) and 60 min after 1.5 mg/kg E by 47% to 14 +/- 8 (p = 0,001) and was unchanged after 5 h., Conclusion: The clinical trial showed that in P with chronic heart failure (NYHA III and IV) the acute increase of Cl and decrease of PC is higher after E than after C. The improvement of hemodynamics lasts longer after i.v. E than i.v.C.

Glycosylation of benzyl-2,3,6-trideoxy-3-trifluoroacetamido-alpha-L-lyxo-h exopyranoside (6) with 3,4-di-O-acetyl-1,5-anhydro-2,6-dideoxy-L-lyxo-hex-1-enitol (1) or 4-O-acetyl-1,5-anhydro-3-O-benzyl-2,6-dideoxy-L-lyxo-hex-1-enit ol (2) in the presence of trimethylsilyl triflate/triethylamine gave alpha-(1----4)-linked disaccharide derivatives 7 and 8, respectively. In the presence of trimethylsilyl triflate only, 3,4-di-O-acetyl-1-O-tert-butyldimethylsilyl-2,6-dideoxy-beta-L-lyxo++ +-hexopyranose (3) and 6 gave mainly 7. Condensation of 1 or 2 with 9, obtained by O-deacylation of 8, afforded benzyl [O-(3,4-di-O-acetyl-2,6-dideoxy-alpha-L-lyso-hexopyranosyl)-(1----4)-O-( 3-O-benzyl-2,6-dideoxy-2,6-alpha-L-hexopyranosyl)-(1----4)-(2,3,6-tri deo xy-3-trifluoroacetamido-alpha-L-lyxo-hexopyranoside)] (11) and its 3''-benzyl analogue 12, respectively.

The value of two-dimensional cross-sectional echocardiography for the estimation of the left ventricular function had been investigated in 241 consecutive patients with suspected coronary artery disease (CAD). The day before left heart catheterization the left ventricular volumes (EDV, ESV) as well as the global left ventricular ejection fraction (EF) were calculated from the RAO-equivalent in the 2D-echo and in addition the classification of the EF was visually performed from different cross-sections. The coronary angiography showed in 208/241 patients hemodynamically effective stenoses (lumen restriction greater than 50%). For 192/208 patients there were diagnostically usable 2D-echograms as well as clinical data over an observation period of 3 years and 7 months. The 2D-echo correspond quite well to the levocardiography for the calculation of the EDV with r = 0.75, with r = 0.85 for the ESV, and with r = 0.80 for the EF. The mere visual evaluation of the EF out of the 2D-echo agreed well in 84% of the cases to the quantitative determination. During the observation period 18/192 patients died; 17/18 of these patients of cardial causes. Out of the patients with normal EF in the 2D-echo only 3.5% died, with slightly reduced EF 10% died. With highly reduced EF mortality was with 40% significantly increased (p less than 0.001). Thus in patients with CAD unfavourable long-time prognosis may be quickly recognized by their markedly reduced left ventricular function in the 2D-echocardiogram, which shows favourable correspondence to invasive data.

A case is reported of right ventricular outflow obstruction caused by hypertrophic cardiomyopathy. The pressure gradient between the inflow tract and the outflow tract of the right ventricle was 84 mm Hg. Resection of the hypertrophic muscle bundles practically eliminated the obstruction leaving only an insignificant subvalvular gradient of 2 mm Hg. Histologic examination revealed cardiac muscle cell hypertrophy and disorganization.