Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men.

OBJECTIVES: The aim of this study was to determine whether the combination of lipid-lowering therapy and vitamin E supplementation improves peripheral endothelial function and whether it is more effective than lipid-lowering therapy alone. BACKGROUND: Endothelium-dependent vasodilation is impaired in coronary and peripheral arteries of patients with hypercholesterolemia. Coronary endothelial function has been shown to improve under lipid-lowering and antioxidant therapy, but the effect of additive vitamin E supplementation in the brachial artery is unknown. METHODS: Seven patients with hypercholesterolemia (mean+/-SD; age 51+/-10 yr) were studied. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent nitroglycerin-induced dilation (NMD) were assessed in the brachial artery using high resolution ultrasound 1) at baseline (BL I), 2) after 8 weeks of simvastatin (20 mg) and vitamin E (300 IU) therapy (Comb I), 3) after withdrawal of vitamin E for 4 weeks (Statin), 4) after therapy as in #2 for 4 weeks (Comb II) and 5) after withdrawal of both drugs for 4 weeks (BL II). RESULTS: Combined simvastatin and vitamin E therapy reduced total cholesterol (Comb I vs. BL I: 276+/-22 vs. 190+/-14 mg/dl, p < 0.0001) and low-density lipoprotein (LDL)-C (197+/-22 vs. 106+/-22 mg/dl, p < 0.00001), augmented alpha tocopherol levels normalized to LDL (12.2+/-4.1 vs. 4.9+/-0.9 microg alpha-T/100 mg% LDL-C, p < 0.01) and resulted in significant improvements in FMD (16.4+/-4.7 vs. 4.9+/-2.5%, p < 0.001) as well as NMD (17.9+/-4.3 vs. 11.2+/-2.8%, p < 0.01). The ratio of FMD to NMD (0.92+/-0.17 vs. 0.46+/-0.24%, p < 0.05) also increased under combination therapy, indicating a greater improvement of FMD than that of NMD. After withdrawal of vitamin E, both FMD (Comb I vs. Statin: 16.4+/-4.7 vs. 7.9+/-4.7%, p < 0.01) and NMD (17.9+/-4.3 vs. 10.9+/-4.5%, p < 0.05) decreased significantly such that simvastatin alone only tended to improve FMD and did not change NMD. Results under combination therapy (Comb II vs. BL II) were reproducible. CONCLUSIONS: Combined vitamin E and simvastatin therapy leads to an improvement of FMD and NMD in the brachial artery of patients with hypercholesterolemia. The improvement of FMD is more pronounced after combination therapy than after lipid-lowering therapy alone, similar to previous findings in the coronary circulation.

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

OBJECTIVES: This 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. BACKGROUND: Coronary 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. METHODS: We 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. RESULTS: Technically 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. CONCLUSIONS: Coronary 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.

Effects of vitamin E on chronic and acute endothelial dysfunction in smokers.

OBJECTIVES: The aims of this study were to determine whether chronic or acute impairment of flow mediated vasodilation (FMD) in the brachial artery of smokers can be restored or preserved by the antioxidant vitamin E. BACKGROUND: Transient impairment of endothelial function after heavy cigarette smoking and chronic endothelial dysfunction in smokers result at least in part from increased oxidative stress. METHODS: We studied 22 healthy male smokers (mean +/- SD, 23 +/- 9 cigarettes per day) randomly assigned to receive either 600 IU vitamin E per day (n = 11, age 28 +/- 6 years) or placebo (n = 11, age 27 +/- 6 years) for four weeks and 11 age-matched healthy male nonsmokers. Flow mediated vasodilation and endothelium-independent, nitroglycerin-induced dilation were assessed in the brachial artery using high resolution ultrasound (7.5 MHz) at baseline and after therapy. Subjects stopped smoking 2 h before the ultrasound examinations. At the end of the treatment period, a third scan was obtained 20 min after smoking a cigarette (0.6 mg nicotine, 7 mg tar) to estimate transient impairment of FMD. RESULTS: Flow mediated vasodilation at baseline was abnormal in the vitamin E (5.3 +/- 3.8, p < 0.01) and in the placebo group (6.4 +/- 3.5, p < 0.05) compared with nonsmoking controls (11.6 +/- 4.7). Using a two-way repeated measures analysis of variance (ANOVA) to examine the effects of vitamin E on FMD, we found no effect for the grouping factor (p = 0.5834) in the ANOVA over time but a highly significant difference with respect to time (p = 0.0065). The interaction of the time factor and the grouping factor also proved to be significant (p = 0.0318). Flow mediated vasodilation values remained similar after treatment for four weeks in both groups but declined faster after smoking a cigarette in subjects taking placebo compared with those receiving vitamin E (p values from successive differences for the time/group factor: 0.0001/0.0017). The transient attenuation of FMD (calculated as the percent change in FMD) was related to the improvement of the antioxidant status, estimated as percent changes in thiobarbituric acid-reactive substances (r = -0.67, p = 0.0024). Nitroglycerin-induced dilation did not differ between study groups at baseline or after therapy. CONCLUSIONS: These results demonstrate that oral supplementation of vitamin E can attenuate transient impairment of endothelial function after heavy smoking due to an improvement of the oxidative status but cannot restore chronic endothelial dysfunction within four weeks in healthy male smokers.

Transesophageal versus intracoronary Doppler measurements for calculation of coronary flow reserve.

OBJECTIVE: The present study was performed to compare coronary flow reserve by transesophageal Doppler echocardiography and intracoronary Doppler flow wire measurements in patients with LAD disease. METHODS: 17 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. RESULTS: Coronary 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. CONCLUSIONS: Coronary flow reserve by both transesophageal techniques correlated with intracoronary Doppler flow wire measurements, however considerable discrepancies may occur in the individual patient.

Effect of lysophosphatidylcholine on atherosclerotic rabbit arteries.

We report here on the effect of an endothelium-dependent vascular smooth muscle relaxant, lysophosphatidylcholine (LPC) on rabbit aortic strips and on hemodynamic changes by LPC in atherosclerotic animals. Cyclic GMP changes induced by LPC in atherosclerotic vessels were also determined. Atherosclerosis was produced by feeding a high cholesterol and saturated fatty acid diet. LPC was injected into the left atrium and coronary flow was measured by radioactive microspheres; in vitro, relaxation of precontracted aortic strips by lysophosphatidylcholine was also recorded. LPC failed to increase coronary flow in the presence of atherosclerosis. In isolated aortic strips, dose-response curves with acetylcholine and LPC showed diminished relaxation in atherosclerotic preparations, and cyclic GMP production following LPC was reduced. The results demonstrate that vascular relaxation by LPC, together with its ability to activate guanylate cyclase is dependent on the functional and morphological integrity of the vascular wall.

Effect of antihypertensive treatment with doxazosin on insulin sensitivity and fibrinolytic parameters.

The effects of the selective alpha-1-adrenoceptor antagonist doxazosin on metabolic and fibrinolytic parameters were studied in hypertensive patients with various degrees of fasting plasma insulin levels (Group A: 22.5 +/- 3 microU/ml, Group B: 8.1 +/- 1.5 microU/ml; p <0.01) to disclose a potential link between a doxazosin-induced alteration of insulin and/or lipid metabolism and possible changes of these parameters on the fibrinolytic system. Doxazosin treatment resulted in a dose-dependent reduction of basal insulin levels in group A to 16 +/- 3 microU/ml; p <0.05. This finding was paralleled by a dose-dependent increase in t-PAmass concentration in the same patient group (basal t-PAmass from 9.7 +/- 1 to 15.5 +/- 2 ng/ml; p <0.05). As PAI-1 "active" as well as total antigen levels were not altered in parallel, the net effect on the endogenous fibrinolytic system is an increase of the fibrinolytic potential.

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.

Emergency aortic valve replacement for critical aortic stenosis. A lifesaving treatment for patients with cardiogenic shock and multiple organ failure.

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.

The ACE-inhibitor lisinopril affects plasma insulin levels but not fibrinolytic parameters.

There is evidence that ACE-inhibitors exert beneficial effects on endogenous fibrinolysis in patients with previous myocardial infarction. It is still unknown if this effect is restricted to this patient group only and by which mechanisms ACE-inhibitors exhibit the profibrinolytic effects. One possible explanation might be the positive influence of ACE-inhibitors on insulin metabolism by decreasing plasma insulin which in turn could decrease PAI-1, a major regulator of the fibrinolytic system. Therefore the present study examines the relationship between insulin and PAI-1 plasma levels during intravenous glucose tolerance tests before and after administration with the ACE-inhibitor lisinopril in 12 male obese patients with angiographically proven coronary artery disease and borderline hypertension. After a 4-weeks wash-out period glucose tolerance tests were performed before and after lisinopril-treatment (10mgs/d) for 12 weeks. After the treatment period, fasting plasma insulin level decreased from 15.6 +/- 2.1 to 11 +/- 1.8 uU/ml, p < or = 0.01. Stimulated levels of insulin during glucose tolerance test also significantly decreased by lisinopril (peak insulin from 57 +/- 10 to 41.2 +/- 7.3 uU/ml, p < or = 0.02). Basal plasma tissue plasminogen activator antigen, PAI-1 total antigen and PAI-1 "active" antigen were unaffected by therapy (8.4 +/- 0.5 vs 8.6 +/- 0.5 ng/ml, 118 +/- 20 vs 124 +/- 16 ng/ml and 21 +/- 7 vs 30 +/- 7 ng/ml, respectively). Our data confirm a beneficial effect of lisinopril on plasma levels of insulin but failed to demonstrate any profibrinolytic effect in this study population, thus questioning the postulated mechanism of influencing endogenous fibrinolysis by changes of plasma insulin.

Stimulating effect of biologically modified low density lipoproteins on ADP-induced aggregation of washed platelets persists in absence of specific binding.

Oxidized low density lipoproteins are closely associated with atherosclerosis and also might be directly involved in thrombosis because they have been shown to mediate a stimulating effect on human platelets. In this work, we used biologically modified low density lipoproteins (i.e., low density lipoproteins sufficiently oxidized to show specificity for the macrophage scavenger receptor system) to examine if specific binding of the oxidized apolipoprotein moiety to the platelet surface is a prerequisite for the platelet-stimulating effects reported by other authors. We find that biologically modified low density lipoproteins show specific binding to human platelets (K(d)=5.83+/-0.4 microg/mL, 3850+/-620 sites/platelet) and strongly augment both ADP- and thrombin-induced aggregation of washed platelets. Maleylated albumin, an antagonist of oxidized low density lipoproteins binding to all currently classified scavenger receptors, is able to reduce platelet oxidized low density lipoproteins binding to background levels. Nevertheless, maleylated albumin is not able to exert any kind of normalizing effect on the augmented ADP-induced aggregation response observed in the presence of biologically modified low density lipoproteins. From these data, we conclude that specific binding of oxidatively modified apolipoprotein B to the platelet surface is not essential to the process of platelet stimulation. Therefore, we conclude that these stimulating effects may be mediated by unidentified compounds formed in the lipid phase of the lipoproteins.

Vascular smooth muscle and nitric oxide.

Experiments were performed to investigate the production of endothelium-derived relaxing factor (EDRF or nitric oxide; NO) by vascular smooth muscle cells. The lumen of bovine pulmonary arteries were filled with Krebs-Henseleit solution (incubates). Both endothelium-intact and endothelium-deprived vessels were used. Incubate solutions from the lumen of generator vessels contained a significant amount of nitric oxide (NO). Although the NO concentration was higher in incubates from endothelium-intact vessels, endothelium-deprived vessels also produced NO. The length of incubation did not influence the amount of nitric oxide released. Endothelium-deprived pulmonary arteries also generated NO as detected by chemiluminescence. The amount produced however was not sufficient to relax endothelium-deprived detector vessels in superfusion bioassay experiments. Samples from Krebs-Henseleit (K-H) solution surrounding the preparation (bathing solution) contained NO values which were also significantly higher than the control. Nitric oxide found in the bathing solution also appeared to originate from endothelium and vascular smooth muscle. Oxyhemoglobin attenuated NO signals. The results demonstrate that nitric oxide is released by vascular smooth muscle cells as well as by endothelium. However, the amount of NO released by muscle is insufficient to relax endothelium-deprived vascular preparations.

A model to study physiological activation of phospholipase A2 and vasorelaxation by lysophosphatidylcholine.

Earlier we demonstrated that micellar solutions of LPC caused endothelium-dependent relaxation of rabbit thoracic aorta and bovine intrapulmonary artery and vein through a cyclic GMP-dependent mechanism. The availability of LPC for vasorelaxation depends on its production by deacylation of PC by PLA2. We assessed the possible activation of PLA2 by commonly used vasorelaxants such as acetylcholine, bradykinin, calcium ionophore A23187 and thrombin and vasoconstrictors like histamine and phenylephrine in the presence of indomethacin in a model system where 14C PC was incorporated into bovine intrapulmonary arterial segments. Taking the ratio of 14C PC:LPC formed by exogenous PLA2 as an index of deacylation, we found that while all the agents relaxed the strips in an endothelium-dependent manner, only thrombin caused relaxation followed by an increase in 14C LPC and a concomittant decrease in 14C PC indicating activation of PLA2. Our data show that PC/PLA2 system can be activated to generate LPC for vascular relaxation under specific physiological conditions. This model system can be used to monitor PLA2 activity and LPC production to compensate flow and pressure induced changes in arteries.

Comparison of transesophageal coronary sinus and left anterior descending coronary artery Doppler measurements for the assessment of coronary flow reserve.

BACKGROUND: Currently used methods for assessment of coronary flow reserve are invasive and require extensive laboratory equipment. Recently, noninvasive assessment of coronary flow reserve by transesophageal Doppler evaluation of coronary sinus (CS) or left anterior descending coronary artery (LAD) flow has been proposed. Direct comparison between these two techniques is lacking. METHODS: Doppler recordings of CS and LAD flow velocity were obtained before and after 0.6 mg/kg/5 min dipyridamole in 16 patients with significant stenosis of the LAD (Group A) and in 14 control patients (Group B). Flow recordings and all measurements were performed in a blinded manner. For assessment of coronary flow reserve, Doppler measurements after dipyridamole were divided by the respective baseline values. RESULTS: Doppler studies of the CS and LAD were feasible in 30 of 30 (100%) and 23 of 30 (71%) patients, respectively. Analyzing the maximum flow velocities, coronary flow reserve in Groups A and B was 1.18 +/- 0.28 and 1.68 +/- 0.53 with CS recordings and 1.78 +/- 0.83 and 2.51 +/- 0.76 with LAD recordings, respectively. Analyzing the velocity time integrals, coronary flow reserve in Groups A and B was 1.53 +/- 0.68 and 2.59 +/- 0.74 with CS recordings and 1.77 +/- 0.38 and 2.68 +/- 0.93 with LAD recordings, respectively. Correlation between LAD and CS recordings was 0.69 (p < 0.001), when coronary flow reserve was calculated from the velocity time integral and 0.68 (p < 0.001) when the maximum flow velocities were used. CONCLUSION: Both transesophageal Doppler techniques might be useful for noninvasive assessment of coronary flow reserve.

Comparison of transesophageal Doppler coronary flow reserve measurements with thallium-201 single-photon emission computed tomography imaging in assessment of left anterior descending artery stenoses.

BACKGROUND AND HYPOTHESIS: Recent studies demonstrate the feasibility of coronary flow reserve measurements by transesophageal echocardiographic (TEE) Doppler recordings of coronary sinus or left anterior descending (LAD) coronary artery flow velocity for detecting stenoses of the LAD artery. This study compares coronary flow reserve measurements by Doppler TEE with thallium-201 (201Tl) single-photon emission computed tomography (SPECT) in patients with proximal single-vessel LAD stenosis. METHODS: Nineteen patients with various degrees of LAD stenosis (mean area stenosis 71 +/- 24%; range 24-96%) were studied. Area stenosis by quantitative coronary angiography was < 75% in 7 patients and > 75% in 12 patients. Transesophageal LAD and coronary sinus Doppler measurements were performed at baseline and after intravenous dipyridamole. Coronary flow reserve was calculated as the ratio of hyperemic to baseline average peak velocities. Predefined coronary flow reserve cut-off values of 1.8 for the coronary sinus method and of 2.0 for the LAD method were used for diagnosis of significant LAD stenosis. Results were compared with qualitative 201Tl dipyridamole SPECT. RESULTS: Overall predictive accuracy for diagnosis of > 75% LAD stenosis was 79% for 201Tl SPECT, 77% for the transesophageal LAD and 79% for the transesophageal coronary sinus technique. Concordant results between 201Tl SPECT and the LAD and coronary sinus Doppler methods were observed in 79% and 71% of patients, respectively. CONCLUSIONS: Thallium-201 SPECT and transesophageal Doppler assessment of coronary flow reserve have similar accuracy for diagnosing significant proximal LAD stenosis. Therefore, both transesophageal Doppler techniques might constitute another widely available, noninvasive method for assessment of left coronary artery disease, if disease location is proximal.

Effects of antihypertensive therapy on glucose and lipid metabolism.

Large epidemiological studies demonstrate only moderate reduction in the incidence of coronary artery disease by antihypertensive drug treatment. This is attributed to the prevalence of multiple risk factors in hypertensive patients and to possible adverse metabolic effects of antihypertensive drugs which may counteract their ability to reduce the risk of cardiovascular disease. The choices for pharmacological blood pressure reduction are divided between five classes with similar antihypertensive efficacy but markedly different influence on coronary risk factors. Hence, the clinician has to consider the prevalence of coexisting coronary risk factors, comorbidity as well as the efficacy, side effects, and mechanisms of drug action.

Myocardial perfusion in patients with typical chest pain and normal angiogram.

BACKGROUND: Approximately 10-30% of patients with typical chest pain present normal epicardial coronaries. In a proportion of these patients, angina is attributed to microvascular dysfunction. Previous studies investigating whether angina is the result of abnormal resting or stress perfusion are controversial but limited by varying inclusion criteria. Therefore, we investigated whether microvascular dysfunction in these patients is associated with perfusion abnormalities at rest or at stress. PATIENTS AND METHODS: In 58 patients (39 female, 19 male, mean age 58+/-10 years) with angina and normal angiogram as well as 10 control patients with atypical chest pain and normal coronaries (six female, four male, mean age 53+/-11 years) myocardial blood flow (MBF) was measured at rest and under dipyridamole using 13N-ammonia PET. Resting MBF and coronary flow reserve (CFR) as the ratio of hyperaemic to resting MBF were corrected for rate-pressure-product (RPP): normalized resting MBF (MBFn)=MBFx10,000/RPP and CFRn=CFRxRPP/10,000. RESULTS: Sixteen/58 patients had a normal CFRn (=2.5; group I; CFRn: 3.1+/-0.88); the same as the controls (CFRn: 3.3+/-0.74). Forty-two/58 patients presented a reduced CFRn (group II; CFRn: 1.78+/-0.57). Group II had both a higher MBFn (group II: 1.30+/-0.33 vs. Group I: 1.03+/-0.26; P<0.05 and vs. controls: 1.07+/-0.19; P<0.01) and a lower hyperaemic MBF (group II: 2.25+/-0.76 mL g-1 min-1 vs. Group I: 3.07+/-0.78 mL g-1 min-1; P<0.001 and vs. controls: 3.41+/-0.94 mL g-1 min-1; P<0.0001). CONCLUSION: Impaired CFRn in patients with typical angina and normal angiogram is owing to both an increased resting and reduced hyperaemic MBF. Therefore, PET represents a prerequisite for further studies to optimize treatment in individuals with anginal pain and normal coronary angiogram.

Severe complications following thrombolytic therapy of an acute thrombosis of a prosthetic mitral valve.

Thrombosis of prosthetic cardiac valves is a rare but potentially lethal complication. As emergency surgical intervention of thrombotic prosthetic cardiac valves is correlated with high mortality, fibrinolytic therapy has been recently recommended as a therapy with high efficacy and no severe side effects. We report on a patient with thrombosis of a prosthetic mitral valve who developed severe embolic complications following the administration of the thrombolytic agent. On admission the patient showed signs of incipient cardiogenic shock. The diagnosis of thrombotic obstruction of the prosthetic mitral valve was confirmed by transesophageal echocardiography. The effective valve area was 0.41 cm2. Pulmonary arterial blood pressure and wedge pressure were significantly elevated. A fibrinolytic therapy with recombinant tissue-type plasminogen activator according to the Neuhaus scheme was attempted. Within 60 min after start of treatment the effective valve area increased (1.41 cm2), and the pulmonary capillary wedge pressure decreased. However, peripheral and cerebral embolism occurred. Occlusion of the right brachial and right femoral artery was ascertained by Doppler ultrasound. Embolism into the right leg made an embolectomy with a Fogarty catheter necessary. Computed tomography revealed two lesions located in the occipital and left temporal area of the brain. Correlated with the lesions evaluated in computed tomography, right hemiplegia and complete aphasia was observed. The neurological status of the patient has only slightly improved to the present. To our knowledge no severe persistent neurological deficits following thrombolytic therapy have been reported. We therefore assume that the risk of severe neurological complications is underestimated.(ABSTRACT TRUNCATED AT 250 WORDS)

An improved chemiluminescence assay suggests non nitric oxide-mediated action of lysophosphatidylcholine and acetylcholine.

Using a new nitric oxide analyser, we have developed a sensitive chemiluminescence assay to detect trace quantities of NO in aqueous solutions. This improved technique in combination with the bioassay has been employed to verify the theory that NO released by vascular endothelium, accounts for the relaxation produced by acetylcholine, lysophosphatidylcholine and calcium ionophore A23187. Our results show that while calcium ionophore A23187 continuously released NO, acetylcholine and lysophosphatidylcholine relaxed vascular strips without releasing NO over the basal level.