Günter Christ

Mean platelet volume is an independent risk factor for myocardial infarction but not for coronary artery disease.

Summary.u2002 After rupture of an arteriosclerotic plaque in a coronary artery, platelets play a crucial role in the subsequent thrombus formation, leading to myocardial infarction. An increased mean platelet volume (MPV), as an indicator of larger, more reactive platelets, may represent a risk factor for myocardial infarction. However, this hypothesis is still controversial and most studies addressing the role of MPV were performed comparing patients suffering from myocardial infarction with healthy controls. We intended to identify patients at high risk of suffering myocardial infarction in a group of patients with known coronary artery disease. One hundred and eighty‐five consecutive patients with stable coronary artery disease were compared with 188 individuals who had suffered myocardial infarction. Patients within the highest quintile of MPV (≥u200311·6u2003fl) had a significantly higher risk of experiencing a myocardial infarction compared with patients within the lowest quintile (ORu2003=u20032·6, 95%u2003CIu20031·3–5·1) in a multivariate analysis that included sex, age, body mass index, hyperlipidaemia, hypertension, smoking and diabetes mellitus. Our results indicate that patients with pre‐existing coronary artery disease and an increased MPV (≥u200311·6u2003fl) are at higher risk of myocardial infarction. These patients can be easily identified during routine haematological analysis and could possibly benefit from preventive treatment.

Estimation of coronary flow reserve by transesophageal coronary sinus Doppler measurements in patients with syndrome X and patients with significant left coronary artery disease

OBJECTIVESnThis study sought to determine the feasibility of coronary sinus flow velocity analysis by transesophageal Doppler echocardiography for estimation of coronary flow reserve in patients with syndrome X and patients with coronary artery disease.nnnBACKGROUNDnCoronary flow reserve provides useful information in patients with coronary artery disease and patients with syndrome X. Current methods of measuring coronary flow reserve are invasive or require extensive laboratory equipment, or both. Transesophageal Doppler recordings of coronary sinus flow velocity before and after vasodilator application may allow noninvasive determination of coronary flow reserve.nnnMETHODSnWe obtained coronary sinus flow velocity recordings before and after dipyridamole administration (0.6 mg/kg body weight per 5 min) in 9 patients with syndrome X, 14 with significant left coronary artery disease and 22 age-matched control patients. We used the formula anterograde minus retrograde flow velocity time integral times heart rate as an index of coronary sinus flow. Coronary flow reserve was calculated by dividing coronary sinus flow variables after dipyridamole administration by the respective baseline values.nnnRESULTSnTechnically adequate recordings were obtained in 44 (98%) of 45 patients. Compared with that in the control group (2.78 +/- 0.95 [mean +/- SD]), coronary flow reserve was significantly lower in patients with syndrome X (1.21 +/- 0.23, p < or = 0.001) as well as in those with coronary artery disease (1.47 +/- 0.7, p < or = 0.001). Using a cutoff coronary flow reserve value of 1.8, sensitivity, specificity and overall predictive value of coronary flow reserve determinations were, respectively, 100%, 91% and 94% for syndrome X and 86%, 91% and 89% for coronary artery disease.nnnCONCLUSIONSnCoronary flow reserve calculation by transesophageal coronary sinus flow velocity recordings is feasible in a large proportion of patients and might be useful for the noninvasive evaluation of patients with syndrome X and patients with severe left coronary artery disease.

Effect of urokinase on the proliferation of primary cultures of human prostatic cells

The effects of exogenously added urokinase type plasminogen activator, tissue type plasminogen activator, plasmin and thrombin on the proliferation of primary cultures of cells derived from prostatic hyperplasia or prostatic carcinomas were investigated by measuring the incorporation of 3H-thymidine into the cultures. Addition of urokinase type plasminogen activator (1.35 x 10(-9) M) or thrombin (10(-7) M) to the culture medium caused a two-fold increase of 3H-thymidine incorporation, regardless of the origin of the prostatic cells. Tissue type plasminogen activator did not alter the rate of 3H-thymidine incorporation, whereas plasmin caused a 25% decrease of 3H-thymidine incorporation in all cultures.

Plasmin Activation System in Restenosis: Role in Pathogenesis and Clinical Prediction?

During recent years it has become increasingly recognized that the plasmin activation system is involved in the development of atherosclerosis and restenosis. Responsible pathophysiologic mechanisms, however, remain elusive. This review focuses primarily on the clinicians, point of view, suggesting that increases in plasminogen activator inhibitor type-1 (PAI-1) plasma levels after balloon angioplasty or permanently elevated lipoprotein (a) (Lp(a)) plasma levels might be helpful in the prediction of restenosis after coronary angioplasty. In contrast, tissue-type plasminogen activator (tPA) plasma levels appear unrelated to restenosis, and data regarding a possible role of urokinase-type plasminogen activator (uPA) in circulation are not available at present. Furthermore, a new hypothesis on the pathophysiological role of local PAI-1 overexpression as a beneficial negative feedback mechanism to limit excess cellular proliferation in atherogenesis and restenosis is presented.

Relation of Hemodynamic Variables to Augmentation of Left Anterior Descending Coronary Flow by Intraaortic Balloon Pulsation in Coronary Artery Disease

Recent studies suggest prophylactic intraaortic balloon-pulsation (IABP) in patients undergoing coronary reperfusion therapy. However, variable effects of IABP on coronary blood flow are reported. It is suggested that augmentation of coronary flow is more effective in patients with a compromised hemodynamic status, which might have potential relevance in selecting IABP treatment in patients undergoing reperfusion therapy.

Transesophageal versus intracoronary Doppler measurements for calculation of coronary flow reserve

OBJECTIVEnThe present study was performed to compare coronary flow reserve by transesophageal Doppler echocardiography and intracoronary Doppler flow wire measurements in patients with LAD disease.nnnMETHODSn17 patients with various degree of LAD stenosis were studied. Intracoronary LAD Doppler measurements were performed at baseline and after intracoronary injection of 18 micrograms adenosine. Transesophageal coronary sinus and LAD Doppler measurements were performed at baseline and after intravenous dipyridamole (0.6 mg/kg/5 min). Coronary flow reserve was calculated as the ratio of hyperemic to baseline average peak velocities.nnnRESULTSnCoronary flow reserve was 2.44 +/- 0.62 and 2.19 +/- 0.76 for proximal and distal intracoronary measurements and was 2.25 +/- 0.64 and 1.74 +/- 0.63 for transesophageal LAD- and coronary sinus measurements. Proximal intracoronary flow reserve significantly correlated with transesophageal coronary sinus (r = 0.73, p < or = 0.001) and LAD (r = 0.70, p < or = 0.005) measurements, whereas distal intracoronary flow reserve only correlated with transesophageal coronary sinus flow reserve (r = 0.56, p < or = 0.02). Receiver operating characteristic curve analysis demonstrated similar diagnostic accuracy of all applied techniques for detection of a significant LAD stenosis.nnnCONCLUSIONSnCoronary flow reserve by both transesophageal techniques correlated with intracoronary Doppler flow wire measurements, however considerable discrepancies may occur in the individual patient.

Emergency aortic valve replacement for critical aortic stenosis

Objective: To demonstrate that emergency aortic valve replacement can be successfully performed in patients with critical aortic stenosis and reduced left ventricular function even in cardiogenic shock with associated severe multiple organ failure. Design: Retrospective, consecutive case series. Setting: Multidisciplinary intensive care unit of a tertiary care university hospital. Patients: Five patients admitted to the intensive care unit with critical aortic stenosis (aortic valve area 0.56 ± 0.13 cm2) and greatly reduced left ventricular ejection fraction (20 ± 3 %) in prolonged cardiogenic shock and associated multiple organ failure (Multiple organ failure score 6.8 ± 0.5; Acute Physiology, Age, and Chronic Health Evaluation III score 91 ± 27). Intervention: Emergency aortic valve replacement. Results: All patients survived with full recovery of organ function. At follow-up (18 ± 10 months) all patients were in New York Heart Association functional class I or II with improvement of left ventricular ejection fraction to 48 ± 25 %. Conclusions: This excellent outcome suggests that emergency aortic valve replacement should be strongly considered in patients with critical aortic stenosis even in cardiogenic shock and multiple organ failure.

Fibrinolytic Parameters in Spermatozoas and Seminal Plasma

Urokinase-type (u-PA) and tissue-type plasminogen activator antigen (t-PA) as well as plasminogen activator-inhibitor activity were determined in seminal plasma and lysates of the respective spermatozoas in 67 ejaculate of males in infertile marriage without genito urinary pathology. U-PA was determined by a competition RIA, t-PA by an ELISA and PAI by a spectrophotometric assay. 15 patients showed normozoospermia, 11 azoospermia and 41 oligoasthenoteratozoospermia (OAT-syndrome). In lysates of spermatozoas, significantly higher levels of both plasminogenactivators and PAI were found in patients with OAT syndrome as compared to those exhibiting normozoospermia. Whereas PAI was absent in the seminal plasma of normozoospermic ejaculate, patients with azoospermia (180 +/- 13 mU/ml.) and OAT-syndrome (60 +/- 5 mU/ml.) showed high PAI levels. The similarly high values of t-PA (190.8-227.8 ng./ml.) and u-PA (19.4-32 ng./ml.) in the same compartment confirm their predominantly prostatic origin and seem to have no influence on the quality of the ejaculate.

Comparative cross-over study of the effects of lisinopril and doxazosin on insulin, glucose and lipoprotein metabolism and the endogenous fibrinolytic system

Summary Objective: The present study was performed to compare the effects of the alpha-1-blocker doxazosin (4 mg/d) with the ACE-inhibitor lisinopril (10 mg/d) in a cross-over study on plasma levels of metabolic and fibrinolytic parameters. Patients, methods: In 10 male patients with upper body obesity, proven stable coronary artery disease and hypertension, measurements included baseline determination of lipoproteins and fibrinolytic parameters and determinations of glucose and insulin during intravenous glucose tolerance tests after two 12-week treatment periods. Results: Basal insulin levels were significantly decreased by both doxazosin and lisinopril (from 15.5±3.5 μU/ml to 11.6±2 μU/ml, P≤0.05 and from 16.5±2.8 μU/ml to 11.2±2.4 μU/ml, P≤0.001; respectively). Lisinopril decreased the area under the insulin-concentration time curve by 31.9% (P≤0.007) as compared to 23.6% (n.s.) after doxazosin treatment. HDL-cholesterol was increased by lisinopril from 38±3.5 to 43.5±4.4 mg/dl (P≤0.05), t-PA antigen was increased by doxazosin from 8.3±0.7 to 11.4±1.6 ng/ml (P≤0.05) and PAI-1 was not affected by either therapy. Conclusion: These potentially favorable effects on insulin and lipid metabolism and the endogenous fibrinolytic system might contribute to a higher efficacy of antihypertensive treatment in patients with coronary artery disease and accompanying metabolic cardiovascular risk factors.

Progression from partial to complete papillary muscle rupture in acute myocardial infarction.

Siri Papillary muscle rupture is a rare and often fatal complication of acute myocardial infarction. Most patients develop pulmonary edema due to acute mitral regurgitation, and 70% of patients deteriorate into cardiogenic shock, with an overall mortality rate of up to 80% [1]. In cardiogenic shock emergency surgical intervention is indicated but is associated with high perioperative mortality [2]. Optimal timing of operation in patients with stable hemodynamics is under discussion [3]. A 77-year old man was admitted with the diagnosis of acute anterolateral myocardial infarction. There was no history of coronary artery disease. Thrombolysis was withheld because the duration of symptoms before admission exceeded 24 h. The patient was stable without signs of left heart failure. Five days later acute pulmonary edema occurred requiring mechanical ventilation. Clinical examination revealed a holosystolic apical murmur. Transthoracie echocardiography showed a normal-sized left ventricle with circumscript akinesia of the lateral wall. Transesophageal echocardiography revealed systolic prolapse of the anterior mitral valve leaflet due to partial rupture of the anterolateral papillary muscle with moderate mitral regurgitation (Fig. 1, upper panel). Under dopamine (3 gg kg 1rain-l) and dobutamine (5 gg kg -I rain -1) cardiac index was 3.21 min -1 m 2, mean arterial blood pressure was 65 mmHg, and mean pulmonary artery occlusion pressure was 15 ram, with a V wave of 19 mmHg. Coronary angiography showed severe three-vessel disease. Intra-aortic balloon counterpulsation was initiated. The patient condition then stabilized. Pulmonary congestion disappeared, and the intra-aortie balloon catheter was removed. On the 10th postinfarction day total atrioventricular block occurred, requiring short term cardiopulmonary resuscitation and transvenous pacemaker stimulation. Cardiogenic shock developed, and intra-aortic counterpulsation was reinstituted. Mean pulmonary occlusion pressure had increased to 35 mmHg, and a V wave of 47 mmHg was present. At this time, multiplane TEE revealed complete rupture of the anterolateral papillary muscle with a flail anterior mitral valve leaflet and severe mitral regurgitation (Fig. 1, lower panel). Emergency mitral valve replacement with concomitant aortocoronary bypass grafting was performed. However, the patient died 24 h postoperatively due to left ventricular failure. Acute myocardial infarction complicated by severe mitral regurgitation and cardiogenic shock requires urgent mitral