[Prevalence of acetylsalicylic acid (ASA) - low response in vascular surgery]. / Prävalenz der ASS-Low-Response in der Gefäßchirurgie.

BACKGROUND: Research has revealed that a decreased antiplatelet effect (low response [LR]/high on-treatment platelet reactivity [HPR]) of acetylsalicylic acid (ASA) and clopidogrel is associated with an increased risk of thromboembolic events. There are extensive ASA low response (ALR) and clopidogrel low response (CLR) prevalence data in the literature, but there are only a few studies concerning vascular surgical patients. The aim of this study was to examine the prevalence and risk factors of ALR and CLR in vascular surgical patients. MATERIALS AND METHODS: We examined n = 154 patients with an antiplatelet long-term therapy, who were treated due to peripheral artery occlusive disease (PAD) and/or arteria carotis interna stenosis (CVD). To detect an ALR or CLR, we examined full blood probes with impedance aggregometry (ChronoLog® Aggregometer model 590). Risk factors were examined by acquisition of concomitant disease, severity of vascular disease, laboratory test results and medication. RESULTS: We found a prevalence of 19.3 % in the ALR group and of 21.1 % in the CLR group. Risk factors for ALR were an increased platelet and leucocyte count and co-medication with pantoprazole. We found no significant risk factors for a decreased antiplatelet effect of clopidogrel treatment. CONCLUSION: The investigated prevalence for ALR and CLR are in the range of other studies, particularly based on cardiological patients. More investigations are needed to gain a better evaluation of the risk factors for HPR and to develop an effective antiplatelet therapy regime to prevent cardiovascular complications.

Influence of glycaemic control on platelet bound CD40-CD40L system, P-selectin and soluble CD40 ligand in Type 2 diabetes.

AIMS: Type 2 diabetes is a potent cardiovascular risk factor, associated with proinflammatory and prothrombotic processes. The purpose of this study was to investigate whether platelet-bound CD40-CD40L signalling, P-selectin expression and soluble CD40L were increased in patients with diabetes mellitus and can be normalized by improving glycaemic control. METHODS: Soluble (s) CD40L, platelet surface expression of CD40L, CD40 and P-selectin (CD62P) on platelets were measured by flow cytometry in 71 patients with Type 2 diabetes mellitus and 37 healthy volunteers. In addition, the relationship of HbA1c to CD40-CD40L and P-selectin expression was determined in a longitudinal follow-up. RESULTS: In patients with Type 2 diabetes, platelet membrane CD40 expression (Type 2 diabetes 3.1+/-0.61 vs. controls 2.5+/-0.85 mean fluorescence intensity; P=0.001), platelet-bound CD40L (1.2+/-0.32 vs. 1.1+/-0.14; P=0.034) as well as surface expression of CD62P (0.66+/-0.19 vs. 0.57+/-0.12; P=0.007) were higher than in control subjects. Plasma sCD40L values (3.2+/-1.70 vs. 1.8+/-0.50 ng/ml; P<0.001) were also significantly increased in Type 2 diabetes. After improving glycaemic control in patients with initial HbA1c>8.5% (n=15), platelet P-selectin and CD40-CD40L expression decreased significantly by 54.0%, 36.22% and 16.26%, respectively 1 year later. CONCLUSIONS: Type 2 diabetes is associated with up-regulation of the platelet-bound CD40-CD40L system, platelet hyperactivity (enhanced P-selectin expression) and increased sCD40L levels. Improved glycaemic control, however, does help to correct abnormal platelet activation via down-regulation of CD40-CD40L system and P-selectin expression.

Patient-prosthesis mismatch and left ventricular remodelling after implantation of Shelhigh SuperStentless aortic valve prostheses.

AIM: Aortic valve replacement is a standard procedure for the treatment of severe aortic valve stenosis. Due to lower flow velocities stentless valves are associated with a more effective regression of left ventricular hypertrophy in comparison to stented valves. However, mismatch between body surface area and valve size supports unfavourable hemodynamic results. The aim of the study was to analyze hemodynamic parameters by echocardiography after implantation of the Shelhigh SuperStentless bioprosthesis and to analyze the occurrence of patient-prosthesis mismatch and left ventricular remodelling in this specific valve type. METHODS: A total of 20 patients with severe aortic stenosis underwent implantation of a Shelhigh Super Stentless prosthesis. Clinical and echocardiographic assessment was done prior to, immediate after and six months after surgery. RESULTS: All surgical procedures were successful, no surgery-related complication was documented perioperatively. One patient died after development of multiorgan failure. Echocardiography during the first eight days after surgery showed mean gradients of 16 mmHg, mean valve orifice areas of 1.8 cm(2) and indexed effective orifice areas at 0.95 cm(2)/m(2). Six-months follow-up data were obtained in 19/20 patients. There were no relevant changes in echocardiographic hemodynamic findings at the time of follow-up measurements. Significant regression of left ventricular hypertrophy was shown (P=0.0088). A patient-prosthesis mismatch occurred in one patient (0.54 cm(2)/m(2)). No recurrent symptoms were documented. CONCLUSION: Patient-prosthesis mismatch after implantation of SuperStentless Shelhigh prosthesis is rare. A significant regression of left ventricular hypertrophy could be shown after six months. Hemodynamic valve function assessed by echocardiography may be predicted early after surgery.

[Angiographic assessment of functionally insignificant left main coronary artery stenoses: reliability compared to intracoronary pressure measurement]. / Angiographische Beurteilung funktionell nicht signifikanter Hauptstammstenosen--Zuverlässigkeit im Vergleich zur intrakoronaren Druckmessung.

BACKGROUND AND OBJECTIVE: Left main coronary artery disease (LMCA) is still a widely accepted indication for coronary artery bypass surgery. Intermediate LMCA disease, however, often cannot be evaluated reliably on the basis of clinical and angiographic information alone. The deferral of surgical revascularization based on fractional flow reserve (FFR) measurements has been shown to be safe and feasible when taking an FFR value of (3) 0.75 as cutoff. This study was performed to compare the accuracy of visual angiographic assessment of intermediate LMCA stenoses by experienced interventional cardiologists with functional assessment by FFR in a patient population with excellent long-term outcome after deferral of surgery on the basis of FFR measurements. PATIENTS AND METHODS: 24 of 51 consecutive patients with intermediate LMCA disease were deferred from surgery based on an FFR value of > or = 0.75. Each angiogram was retrospectively reviewed independently by three experienced interventional cardiologists. Reviewers were blinded to initial FFR results, clinical data, and clinical outcome and asked to classify each lesion as SIGNIFICANT (FFR < 0.75), NOT SIGNIFICANT (FFR > or = 0.75), or UNSURE if the observer was unable to make a decision based on the angiogram. RESULTS: Mean follow-up was 29 +/- 13.6 months. No death or myocardial infarction was observed, event-free survival was 69 %. When taking the "unsure" classifications into consideration the individual reviewers achieved correct lesion classification with respect to FFR results on average in 58 % to 82 % of cases. Interobserver variability resulted in only 46 % of cases in concordant lesion classification (3 agreements or 2 agreements and 1 "unsure" evaluation). The number of concordant agreements between the individual pairs of reviewers did not exceed the rate of coincidental agreements that could be expected to result from simple guessing (mean KAPPA coefficient 0.04). More than 50 % of patients with excellent long-term outcome after deferral of surgery would potentially have undergone operative revascularization if consensual decision making had been solely based on angiographic lesion assessment. CONCLUSION: The functional significance of intermediate or equivocal LMCA lesions should not be based on visual assessment alone, even when performed by experienced interventional cardiologists.

[Acute cardiovascular reactions to cervical nerve root infiltration]. / Akute Herz-Kreislaufreaktionen bei zervikaler Spinalnervenanalgesie.

AIM: The frequency of cardiovascular adverse effects of cervical nerve root infiltration was investigated by means of a prospective study. METHOD: The hemodynamic and respiratory parameters systolic and diastolic blood pressure, heart rate, respiratory rate and oxygen saturation were monitored continuously in 56 patients undergoing cervical spine nerve root infiltration (injection of 10 ml Lidocain 0.5 %, mean depth of injection 5 cm). The monitored time frame ranged from 5 minutes before to 10 minutes after its administration, an additional holter-monitoring began 1 day prior to the injection. RESULTS: Severe complications such as syncopes were not observed in any of the 56 patients, 4 patients developed presyncopes. None of the registered parameters showed a significant change. In a group of patients with known, pre-existing cardiovascular morbidity, no significant changes occurred either. No relevant cardiac arrhythmias were observed. CONCLUSION: The observed cardiovascular complications were not severe. Most probably, the observed reactions were vasavagal presyncopes. Supine positioning led to immediate recovery in all of these patients. A complete hemodynamic monitoring and the placement of an intravenous line do not seem to be absolute necessities in the routine cervical nerve root infiltration.

Mechanical and optical characteristics of a new fiber optical system used for cardiac contraction measurement.

In order to obtain a better physiological performance and a closer restoration of the regular rhythm of failing hearts, a new fiber optical sensor system for the measurement of cardiac contraction has been developed. It consists of an opto-electrical unit and a sensing fiber which has to be positioned in the heart. The objective of this new fiber optic sensor system is to use the inotropic information to adjust a stimulation algorithm in single or multichamber pacing or to detect arrhythmia in insufficient heart function. In this study, the mechanical and optical characteristics of different fibers are investigated. The relationship between the attenuation (with an achieved numerical maximum of 0.3 dB), the bending diameter and the angle of bending is determined in a range of 20-160 mm. The most suitable fiber for the application in cardiological problems is determined (WT8 fiber), for which the sensitivity is analyzed. Additionally, power spectra are calculated from WT8 fiber signals obtained from pig hearts, working under physiological conditions. The maximal frequency response was 23 Hz. It is concluded that the fiber optical measurement of cardiac contraction is not only feasible and reproducible, but the WT8 fiber also shows optimal behavior in the range of parameters occurring in the heart chambers. Nevertheless, in order to restrict the measured signal reliably to bending processes within the chambers only, it is concluded that a special combined fiber has to be constructed with a high sensitivity only at its terminal section within the heart.

Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically important?

In the UGDP study, published in the 1970s, a high incidence of cardiovascular mortality was found in patients treated with the sulfonylurea agent tolbutamide. Impaired ischaemic preconditioning is presumed to be the most important mechanism for the excess cardiovascular mortality observed. However, as tolbutamide has only a low affinity for cardiac sulfonylurea receptors, interference with ischaemic preconditioning seems unlikely to account for this excess mortality. Several smaller studies also failed to establish a definite link between sulfonylurea treatment before acute myocardial infarction and in-hospital mortality. However, when the myocardium becomes exposed to repeated or prolonged periods of ischaemia, ischaemic preconditioning may become clinically important. Myocardial ischaemia can also develop during emergency or elective angioplasty and during coronary bypass surgery. Therefore discontinuation of sulfonylurea treatment should be considered in these circumstances.

[Intraoperative cooled-tip radiofrequency ablation in patients with atrial fibrillation undergoing open heart surgery]. / Sicherheit und Effektivität der intraoperativen gekühlten linearen Hochfrequenzstromablation bei Patienten mit Vorhofflimmern während eines kardiochirurgischen Eingriffs.

METHODS: A total of 113 patients with chronic permanent (104) or paroxysmal (9) atrial fibrillation underwent open heart surgery plus an additional antiarrhythmic procedure using saline-irrigated cooled-tip radiofrequency ablation (SICTRA) for biatrial or left atrial linear lesions. Ablation was performed with steps of short (5 seconds) ablation around the pulmonary vein ostia and interconnecting lines. Postoperative complications and conversions to sinus rhythm were followed up (mean follow-up duration 17+/-14 months). RESULTS: Of the 113 patients, 16 died during follow-up (day 3 up to 33 months) resulting in a cumulative survival of 79% (2 sudden cardiac deaths, 2 gastrointestinal bleedings, 1 renal bleeding, 2 mediastinitis, 1 endocarditis, 1 hemorrhagic insult, 2 respiratory insufficiencies and 2 unknown). Three patients died between day 3 and 6 (30-day mortality 3%) due to low cardiac output. Complications occurred in 19% of the patients including 4% bleeding, 1% pneumothorax, 3% sternal dehiscence, 3% reversible low cardiac output, 6% reversible respiratory insufficiency, 2% TIAs and 1% intra aortal balloon pump implantation. Conversion to sinus rhythm usually occurred spontaneously within 6 months resulting in a cumulative percentage of 80% in sinus rhythm. In these patients, 85% showed biatrial contraction. CONCLUSIONS: SICTRA to treat atrial fibrillation can safely and effectively be combined with different surgical procedures. Mortality and complication rates are comparable to cardiac surgery without antiarrhythmic procedures. No severe procedure-related complications were noted when a stepwise ablation approach during open heart surgery was used. Antiarrhythmic surgical procedures are highly effective in restoring sinus rhythm in patients with atrial fibrillation. Is a modified approach using intraoperatively cooled-tip radiofrequency ablation to induce linear lesions safe and effective in the treatment of atrial fibrillation in cardiosurgical patients?

[Blood gas regulation in isolated beating pig hearts]. / Blutgasregelung bei isoliert schlagenden Schweineherzen.

Continuous perfusion with oxygenated blood is required to supply isolated beating pig hearts. To meet physiological conditions the blood gas parameters pH, pO2 and pCO2 should correspond with values usually found in pigs, respectively. Controlling these parameters manually is a very time consuming task and is therefore done best by a control system consisting of gas blender, oxygenator and blood gas sensors. As this control system should be used with an transportable perfusion apparatus, this paper describes an approach where the gassing is realized only with air and oxygen. In this approach pO2 and pH are measured on blood side so that the control system can change oxygen concentration and gas flow adequately on the gas side.

Minimally invasive coronary artery revascularization on the beating heart.

BACKGROUND: The quality of surgical beating heart revascularization is frequently questioned, especially when the surgical access is limited. Nevertheless, the number of off-pump coronary procedures is expanding worldwide. METHODS: Since getting started with minimally invasive direct coronary artery bypass to anterior myocardial vessels in June 1996, 306 patients received left internal mammary artery grafting through an anterior minithoracotomy. Risk increasing comorbidities were present in 168 of them. Particular attention was paid to early postoperative angiographic results and complications. RESULTS: The 30-day mortality summed up at 1.0% and was limited to patients with additional risks for conventional bypass grafting. Early postoperative control angiographies in 232 patients confirmed a global patency rate of 97.8%, revealing in addition four unexpected malinsertions to diagonal branches. In surviving patients major complications like myocardial infarction, stroke, or multiorgan failure were completely absent. CONCLUSIONS: Minimally invasive direct coronary artery bypass grafting appears to allow for a safe and effective revascularization of the left anterior descending artery by use of the left internal mammary artery. Especially patients with risk increasing comorbidities should benefit from this approach, provided the surgical indication based on a dominating left anterior descending artery lesion. Angiographic minimally invasive direct coronary artery bypass results seem to fulfill the expectations generated by results obtained in conventional left internal mammary artery grafting and appear to be superior to interventional means.

Myocardial "hybrid" revascularisation with minimally invasive direct coronary artery bypass grafting combined with coronary angioplasty: preliminary results of a multicentre study.

OBJECTIVE: To expand the benefits of the minimally invasive direct coronary artery bypass (MIDCAB) concept to patients with multivessel disease, a hybrid procedure combining surgical revascularisation of the left anterior descending artery with interventional procedures for additional coronary lesions has recently been introduced. Preliminary results in patients undergoing this hybrid procedure are presented. DESIGN AND PATIENTS: Since December 1996, 35 patients (29 male, 6 female, mean (SD) age 56.7 (17) years) underwent a hybrid revascularisation performed as a primary MIDCAB procedure for grafting of the left anterior descending artery with the left internal mammary artery, followed by staged angioplasty and stenting of additional coronary lesions. RESULTS: After MIDCAB grafting the postoperative course was uneventful in all patients. Coronary reangiography after a median of seven days revealed patent and functioning left internal mammary artery grafts in all patients. Applying subsequent percutaneous transluminal coronary angioplasty and occasional stenting (n = 14), a total of 47 lesions were treated successfully. Procedure related complications did not occur. All patients remained free from angina and no stress ECG changes were recorded. CONCLUSIONS: The preliminary results of this hybrid approach to myocardial revascularisation suggest that this is a safe and effective procedure for complete revascularisation in selected patients with multivessel disease. Elderly and reoperative patients with significant comorbidity may benefit especially from such hybrid procedures by avoiding cardiopulmonary bypass and mid sternotomy.

[Hybrid technique for myocardial revascularization: value of combined minimal invasive bypass technique (MIDCAB) with interventional therapy (PTCA)]. / Hybrid-Verfahren zur Myokardrevaskularisation: Stellenwert der Kombination von minimal-invasiver Bypasstechnik (MIDCAB) mit interventioneller Therapie (PTCA).

BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) grafting without cardiopulmonary bypass (CPB) through an anterolateral minithoracotomy has become a promising therapeutical option especially in multimorbid, elderly and reoperative patients with single vessel disease. However, this procedure precludes complete revascularization in multivessel disease because the minithoracotomy limits the surgical access either to anterior or lateral or posterior vessels of the beating heart. To expand the benefits of the MIDCAB concept to patients with multivessel disease, new interdisciplinary approaches have recently been introduced. METHODS: Since December 1996, 26 patients (21 male, 5 female, mean age 56.6 +/- 18.8 years) underwent a "hybrid" revascularization performed as a primary MIDCAB procedure for grafting of the left anterior descending artery (LAD) with the left internal mammary artery (LIMA) followed by staged angioplasty and stenting of additional coronary lesions. RESULTS: After MIDCAB grafting, the postoperative course was uneventful in all patients. Coronary re-angiography after a median of 7 days revealed patent and functioning LIMA grafts in all patients. Applying subsequent percutaneous transluminal coronary angioplasty (PTCA) and occasional stenting (n = 8), a total of 31 lesions were treated successfully. Procedure related complications did not occur. All patients remained angina-free and no stress electrocardiographic changes were recorded. CONCLUSION: Our preliminary results of a "hybrid" approach to myocardial revascularization suggest that this concept is a safe and effective approach of complete revascularization for selected patients with multivessel involvement. Especially elderly and reoperative patients with significant comorbidity may benefit from hybrid procedures avoiding cardiopulmonary bypass and midsternotomy.

Incomplete expansion of Palmaz-Schatz stents despite high-pressure implantation technique: impact on target lesion revascularization.

Improved expansion of stents using high-pressure implantation technique with subsequent antiplatelet therapy has improved patient outcome regarding the incidence of subacute stent thrombosis, bleeding complications and restenosis. Whether high-pressure implantation per se guarantees adequate stent expansion remains unclear. The aim of the study was to determine (1) stent expansion after high-pressure implantation technique and (2) whether stent expansion influences rate of target lesion revascularization within 6 months of follow-up. One hundred Palmaz-Schatz stents were implanted in 98 lesions (91 native vessels, 7 graft vessels) of 94 patients using high-pressure implantation technique (balloon pressure 12-20 atm). Stent expansion was investigated using intravascular ultrasound imaging (IVUS). Clinical follow-up of the patients was performed for 6 months. After implantation, stent/mean reference ratio was 0.81 +/- 0.16. Noncompliant balloons used for implantation were chosen by angiographic criteria. Mean balloon/reference ratio was 1.08 +/- 0.22; therefore balloons were not undersized. Additional balloon dilataion using higher pressures and/or larger balloons based on IVUS criteria and subsequent IVUS measurements was performed in 52 patients (55%); in these patients, stent expansion improved from 79 +/- 16 to 91 +/- 15% (mean +/- SD) of average reference areas (p < 0.002). Within the 6 months' clinical follow-up, target lesion revascularization was performed in 19 patients (20%). The only prognostic factors for the development of in-stent restenosis requiring target lesion revascularization were the vessel size (p < 0.05) and the extent of plaque distal to the stents (p < 0.05). Implantation of Palmaz-Schatz stents using high-pressure technique does not guarantee adequate stent expansion. Additional dilatation with higher pressures and/or larger balloons improves stent expansion. The size of the stented vessel and the extent of plaque at the distal stent end (residual outflow stenosis) but not the degree of stent expansion were predictors for target lesion revascularization within 6 months' follow-up.

Early angiographic results after revascularization by minimally invasive direct coronary artery bypass (MIDCAB).

OBJECTIVE: Anastomosing the left anterior descending artery (LAD) by use of the internal mammary artery (IMA) via an anterior minithoracotomy represents the most commonly performed minimally invasive direct coronary artery bypass (MIDCAB). However, little is known about angiographic results beyond patency rates. METHODS: Therefore, a retrospective analysis of 205 consecutive control angiographies was performed evaluating anastomototic patency as well as the angiographic morphology of the left IMA and the LAD. RESULTS: The overall anastomotic patency rate was 98.0%. As a result of incomplete IMA preparation (6-15 cm) large side branches (n = 4), or an IMA course under tension (n = 6) were occasionally observed. Despite a tension-free course, the IMA appeared fixed to the chest wall without functional compromise in 21 cases. A restrictive thrombus formation occurred once, IMA dissection was not seen. Two of the grafts developed spasms. A distal IMA stenosis >50% was seen in five cases. Stenosis of the anastomosis (>50%) itself was found once, as well as unexpected malinsertation to diagonal branches (n = 4). Compared with preoperative angiograms, de novo stenoses of the LAD were assessed proximal (14< or =50%, 2>50%) and distal (15< or =50%, 2>50%) to the anastomosis. Elevation of the LAD out of the vascular bed was an additional finding (n = 12) in a few cases. CONCLUSIONS: The overall patency of MIDCAB-LAD-grafting appears to be equivalent to conventional IMA grafting to the LAD. Particular angiographic findings, however, may be directly associated to the applied surgical technique.

Role of Ca2+-ATPase inhibitors in activation of cytosolic phospholipase A2 in human polymorphonuclear neutrophils.

In the present study, we investigated the involvement of Ca2+-signaling and protein kinases in the effect of Ca2+-ATPase inhibitors on the activation of cytosolic phospholipase A2 (cPLA2) in human polymorphonuclear neutrophils. We found that activity and mobility on electrophoresis gels of the cPLA2 protein were significantly increased by f-Met-Leu-Phe (fMLP), 12-myristate 13-acetate (PMA) and the Ca2+-ATPase inhibitors, thapsigargin and cyclopiazonic acid. This effect was completely suppressed by staurosporine. Calphostin C partially inhibited the fMLP- and PMA-induced cPLA 2 activation, but had no influence on thapsigargin- and cyclopiazonic acid-treated cells. Thapsigargin and cyclopiazonic acid also showed no effect on protein kinase C activity. However, the thapsigargin- and cyclopiazonic acid-induced cPLA2 activation was completely inhibited by the tyrosine kinase inhibitor, erbstatin, and Ca2+ chelator, EGTA. In addition, the cPLA2 activity was reduced after pretreatment with the mitogen-activated protein kinase kinase inhibitor PD98059. The arachidonic acid release was significantly reduced in cells pretreated with the cPLA2 inhibitor, AACOCF3. Furthermore, we found that the human neutrophil cPLA2 cDNA contain a Ca2+-dependent-lipid binding domain which shares homology to several other enzymes such as protein kinase C and phospholipase C. Our results suggest that tyrosine kinases and the MAP kinase cascade are involved in Ca2+-ATPase inhibitor-induced activation and phosphorylation of cPLA2. Protein kinase C is not required in this event.

17Beta-estradiol acutely improves endothelium-dependent relaxation to bradykinin in isolated human coronary arteries.

Improvement of endothelial function has been implicated in the cardioprotective effects of estrogens in women. In isolated human coronary arteries, we investigated whether 17beta-estradiol affects endothelium-dependent responses to bradykinin, an endothelium-derived vasodilator locally produced by endothelial cells. Concentration-response curves to bradykinin (0.03-300 nM) or nitroglycerine (0.01-1 microM) were obtained before and after 30 min of incubation with 17beta-estradiol (3 microM) or solvent control (ethanol 0.2% vol/vol). Incubation with 17beta-estradiol enhanced relaxations to bradykinin (from 43 +/- 6 to 83 +/- 3%, P < 0.0001) but not those to nitroglycerine (n.s.). Improvement of bradykinin-mediated endothelium-dependent relaxation may represent a novel mechanism contributing to the cardioprotective effects of estrogen in women.

Involvement of tyrosine kinases, Ca2+ and PKC in activation of mitogen-activated protein (MAP) kinase in human polymorphonuclear neutrophils.

1. Activation of mitogen-activated protein (MAP) kinase is an early response to a wide variety of stimuli and plays an important role in the regulation of cellular functions. In the present study we investigated the activation of MAP kinase in human polymorphonuclear neutrophils (PMNs). 2. Activity of MAP kinase and protein kinase C (PKC) was measured radiometrically from the rate of phosphorylation of specific peptide substrates. Protein phosphorylation was measured by immunoprecipitation and Western blot analysis. 3. N-Formyl-Met-Leu-Phe (fMLP), phorbol 12-myristate, 13-acetate (PMA) and the Ca2+-ATPase inhibitors thapsigargin (Tg) and cyclopiazonic acid (CPA) increased MAP kinase activity significantly. The tyrosine kinase inhibitors erbstatin and herbimycin A partially inhibited the effects of fMLP and PMA, and completely abolished the effects of both Tg and CPA. The specific PKC inhibitor calphostin C suppressed activation of MAP kinase produced by fMLP and PMA, but had no effect on that produced by Tg and CPA. Tg and CPA were without effect on PKC activity. 4. Immunoprecipitation and Western blot analysis indicated that the 42 and 44 kDa tyrosine-phosphorylated proteins found after stimulation of PMNs were both members of the MAP kinase family. Pretreatment of PMNs with staurosporine, EGTA or erbstatin significantly reduced the tyrosine phosphorylation of MAP kinase(s). 5. These results suggest that in human PMNs, MAP kinase can be stimulated in both a PKC-dependent and a PKC-independent manner. The Ca2+ signal leads to activation of tyrosine kinases, which contribute to the activation of MAP kinase. However, a PMA-sensitive Ca2+-independent pathway also exists. Mobilization of Ca2+ and activation of PKC synergistically induce maximal MAP kinase activation and tyrosine phosphorylation.

Dislodgement of a Wiktor stent during intracoronary ultrasound examination.

We report a case of stent dislodgement complicating adjuvant intracoronary ultrasound (ICUS) imaging that required emergency coronary bypass grafting. This probably very rare complication gains importance since ICUS is increasingly used to confirm adequate stent expansion and full coverage of the lesion.

Contractile responses to histamine, serotonin, and angiotensin II are impaired by 17 beta-estradiol in human internal mammary arteries in vitro.

There is accumulating evidence that estrogen replacement therapy protects against the development of coronary atherosclerosis and myocardial infarction in postmenopausal women. The mechanism of this protective effect is uncertain. The purpose of the present study was to determine whether 17 beta-estradiol acutely modifies vascular smooth muscle contractile responses to various agonists in human arteries in vitro. Human mammary artery rings were obtained during aortocoronary bypass operations. Rings were suspended in organ baths for isometric tension measurements. Concentration response curves induced by serotonin (0.01-30 mumol/l), histamine (0.01-300 mumol/l), and angiotensin II (0.1-100 nmol/l) were generated after pre-incubation for 30 min with either 17 beta-estradiol (3 mumol/l) or solvent (0.2% ethanol). The presence of 17 beta-estradiol significantly reduced the maximal contractile effects induced by histamine, serotonin, and angiotensin II, but not by 80 mmol/l potassium chloride. It is concluded that short-term incubation with 17 beta-estradiol reduces the maximal contractile responses to serotonin, histamine, and angiotensin II. These modulating effects of estrogen on vascular tone may contribute to the proposed beneficial role of estrogen replacement therapy on the incidence of myocardial infarction in postmenopausal women.

[Severe stenosis of the right coronary artery in a 15-year-old girl with type IIa hypercholesterolemia: successful treatment with stent implantation]. / Hochgradige Stenosierung der rechten Koronararterie bei einem 15jährigen Mädchen mit Hypercholesterinämie Typ IIa: erfolgreiche Behandlung durch Stentimplantation.

Coronary artery stenosis with need for therapy is rarely seen in childhood. A 15-year-old girl with hypercholesterinaemia type II a was undergoing lipid aphereses therapy (once or twice a week) since she was 6 years old. The girl was seen in our hospital with stenocardia and depression of the ST-segment in the inferior ECG leads at rest. Myocardial scintigraphy with technetium 99 showed an ischemia of the infero-lateral left ventricular myocardium. During selective coronary angiography a 90% stenosis of the proximal right coronary artery over a distance of approximately 5 mm close to the ostium was found. Post stenotic dilatation of the vessel was obvious. In addition a diffuse 10% stenosis in the proximal and middle part of the right coronary artery was found. The left coronary artery appeared angiographically normal. After balloon dilatation, stent implantation was performed without complications with a 6 mm microstent. Reduction of the stenosis from 90% to 40% could be achieved. Ticlopidin 2 x 250 mg was started for thrombocyte aggregation inhibition. During the following 12 months the patient has been free of symptoms. Lipidaphareses has been continued as before. Stent implantation seems to be a successful treatment for coronary artery stenosis also in young patients.