Harald Kritz

Passive smoking and platelet thromboxane.

While active smoking is known to enhance platelet thromboxane production, no data on passive smoking is available yet. The influence of single and repeated exposure to passive smoke for 60 minutes in a 18 m3 room was assessed in non-smokers as compared to sex and age matched smokers. All the evaluated measures (malondialdehyde, plasma thromboxane B2, 11-dehydro-thromboxane B2, serum thromboxane B2, conversion of exogenous arachidonic acid to thromboxane B2 and to hydroxy-5, 8,10-heptadecatrienoic acid) were higher in smokers than non-smokers at baseline, immediately and 6 hours after passive exposure to cigarette smoke. Repeated exposure of non-smokers rendered their platelets more activated becoming close to the behaviour of smokers. These results indicate that passive smoking may activate thromboxane A2 release from the platelets, contributing to the development of hemostatic imbalance.

The economy class syndrome--a survey of 19 cases.

BACKGROUND Thromboembolic events during or immediately after long-distance flights (economy class syndrome--ECS) are gaining more importance due to the rapidly increasing number of flights. Systematic data on haemostatic parameters in these patients are not available yet. PATIENTS AND METHODS We were therefore analyzing the anamnestic, laboratory and clinical findings in 19 patients (17 males, 2 females, aged 33-75 years) with the final clinical diagnosis ECS. RESULTS Symptoms commenced either immediately or up to 93 hours after disembarkation (mean 42.3 hours). In the great majority (84.2%) myocardial infarction was the initial diagnosis. No defect in the coagulation and/or prostaglandin system was discovered in either of the patients. Prevalence of smoking (26.3%) was even lower than in the normal population. No predisposing factors were found. Apparent anamnestic similarities were flu and fever (47.4%) while 4 of the patients (26.3%) had severe diarrhoea and dehydration before the flight. Almost all the patients (78.9%) were drinking alcohol during the flight and not actively moving their legs (84.2%). ECS occurred also in business and first class passengers. CONCLUSION Surprisingly the onset of ECS is definitely not associated with haemostatic defects and not necessarily associated with the clinical risk factors reported.Background: Thromboembolic events during or immediately after long-distance flights (economy class syndrome – ECS) are gaining more importance due to the rapidly increasing number of flights. Systematic data on haemostatic parameters in these patients are not available yet. Patients and methods: We were therefore analyzing the anamnestic, laboratory and clinical findings in 19 patients (17 males, 2 females, aged 33–75 years) with the final clinical diagnosis ECS. Results: Symptoms commenced either immediately or up to 93 hours after disembarkation (mean 42.3 hours). In the great majority (84.2%) myocardial infarction was the initial diagnosis. No defect in the coagulation and/or prostaglandin system was discovered in either of the patients. Prevalence of smoking (26.3%) was even lower than in the normal population. No predisposing factors were found. Apparent anamnestic similarities were flu and fever (47.4%) while 4 of the patients (26.3%) had severe diarrhoea and dehydration before the flight. Almost al...

Effect of isradipine on in-vivo platelet function.

In animal studies calcium channel blockers (CCBs) and especially isradipine, a second generation dihydropyridine, interrupt the sequence of events culminating in the formation of atherosclerotic lesions. The effect of 4 weeks isradipine treatment (5mg daily) on blood pressure and in-vivo platelet function (measured with 111Indium-oxine labeled autologous platelets) were investigated in a randomized, double-blind and placebo controlled trial in 40 patients with mild to moderate hypertension and scintigraphically diagnosed active atherosclerotic lesions of the carotid arteries. The average supine systolic/diastolic blood pressure was significantly reduced at the end of the treatment period in the isradipine group (group 1; p < 0.0001) but remained unchanged in the placebo group (group P). The heart rate was not significantly altered in either group. There were no serious side effects. The platelet uptake ratio (PUR) measured over the atherosclerotic region of the carotid artery on 4 consecutive days before and after treatment decreased significantly in group I from 1.20 to 1.15 (within groups: p < 0.0001) but remained unchanged in group P. Platelet survival increased significantly in group I (mean 5.70 hours, lower quartile 4.50, upper quartile 4.50 hours, within groups: p < 0.0001) and remained unchanged in group P. Isradipine has a beneficial effect on in-vivo platelet function as evidenced by a decreased platelet deposition on vascular lesion sites and an associated prolonged platelet survival in patients with hypertension and active atherosclerotic lesions.

Antiplatelet activity of semotiadil fumarate

Calcium antagonists are known to exert antiplatelet activity. Semotiadil fumarate (SD-3211), a new benzothiazine, was therefore examined for its antiplatelet activity. The inhibitory activity on adenosine diphosphate (ADP)-, collagen-, arachidonic acid (AA)-, and platelet activating factor (PAF)-induced platelet aggregation after the 1-, 30-, 60- and 120-min incubation at concentrations ranging from 1 x 10(-3), 1 x 10(-4), 1 x 10(-5), 1 x 10(-6) and 1 x 10(-7) was examined. The data were compared with those using diltiazem, nifedipine and amlodipine under identical conditions in blood from eight healthy volunteers (four males, four females; aged 23-36 years) and eight hypertensive patients (four males, four females; aged 31-46 years). Semotiadil showed a dose-dependent inhibition of platelet aggregation in vitro with all the agents examined. Using the various aggregation-inducing agents, the dose-dependent inhibitory action was comparable for all the compounds tested. The antiaggregatory potency was in the order diltiazem, semotiadil, amlodipine and nifedipine. The incubation period did not significantly affect the antiaggregatory effect. No difference between platelets derived from healthy volunteers and hypertensive patients was noted. These findings indicate potent antiplatelet activity of the new calcium antagonist semotiadil.

Isradipine lowers human arterial low density lipoprotein retention in vivo

During the recent past it has been discussed that calcium antagonists may exert antiatherosclerotic actions at the vessel wall. Apolipoprotein B containing lipoproteins were isolated by immunoaffinity chromatography and radiolabeled with 123-iodine. The effect of 2 x 2.5 mg isradipine on the low density lipoproteins (LDL) entry into the carotid and femoral arteries of 12 hypertensive patients with primary hyperlipoproteinemia (total cholesterol >6.5 mmol/l [250 mg/dL) was examined. Cholesterol -1.7% (P< 0.05 664), high density lipoprotein (HDL) cholesterol +4.5% (P< 0.01 123), and LDL cholesterol -1% (P< 0.01 563) did not change, nor did any of the safety parameters. The types of entry kinetics reflecting vascular surface lining did not change while the LDL retention 20 h after tracer application was depressed by up to 23.5%. The data were comparable in the carotid and femoral artery segments, the significance level ranging up to 0.0009. These results indicate a decreased LDL retention in the arterial wall of hypertensive patients induced by isradipine. The clinical implications of the findings ought to be pursued in properly designed clinical trials.

Prostaglandin E1 decreases human arterial accumulation of radiolabeled apo B-containing lipoproteins in vivo

AbstractObjective: An increased apo B-containing lipoprotein influx and cholesterol ester accumulation in arteries are well-known events in human atherogenesis. In vitro and experimental animal studies have provided evidence of a beneficial effect of PGE1 on both vascular apo B-containing lipoprotein accumulation and cholesterol ester content. Methods: We examined the effect of PGE1 (administered via an intravenous portable infusion pump at a rate of 5 ng PGE1 kg−1 ·  min−1 for 5 days a week, 6 h daily, over a total of 5 weeks) in ten patients (eight males, two females) on 123I-apo B-containing lipoprotein accumulation into the large arteries in vivo. Apo B-containing lipoprotein isolation was carried out by immunoaffinity chromatography and radiolabeling with the iodine monochloride method. 123I-apo B-containing lipoprotein accumulation was imaged and quantified by means of special computer software before and after 5 weeks of PGE1 therapy Results: PGE1 led to a significant decrease in maximal arterial apo B-containing lipoprotein retention. The mean decrease in the carotid and femoral arteries in type I lesions amounted to between 16.9% and 30.4%, and in type II lesions between 22.4% and 30.7%, 20 h after injection of radiolabeled apo B-containing lipoprotein. The type of arterial apo B-containing lipoprotein kinetic curves, however, remained unchanged. Conclusion: These findings indicate that PGE1 decreases the apo B-containing lipoprotein influx in the large arteries and the vascular cholesterol content, suggesting that PGE1 may lead to regression of lipid-rich lesions in human in vivo.

Is a(n inborn) deficiency of prostacyclin synthesis stimulating plasma factor associated with increased lipoprotein(a)

Patients with the antiphospholipid syndrome as well as those with a lack in the prostacyclin synthesis stimulating plasma factor (PF) are prone to develop thrombophilia and are at a higher clinical risk for vascular disease. As patients with the antiphospholipid syndrome have been reported to show elevated lipoprotein (Lp)(a) levels, we re-examined all our patients known to have an inborn or an acquired persistent deficiency of PF. Their non-affected relatives served as controls. In addition, 36 patients suffering from clinically manifested atherosclerosis as well as 16 healthy adults, all of them having elevated Lp(a) levels (> 30 mg/dl), were screened for a PF deficiency. In fact, all the patients with a deficient PF activity showed elevated Lp(a) values. While the prevalence of PF deficiency ranges about 1-2%, in 7 (19%) patients with clinically manifested atherosclerosis and 3 (19%) healthy adults with elevated Lp(a) this defect was found. The findings demonstrate an association between PF deficiency and Lp(a), indicating a biochemical interaction which needs to be further elucidated.

PROSTAGLANDIN I2-MEDIATED UPREGULATION OF 125I-LDL-RECEPTOR BINDING BY ISRADIPINE IN NORMO- AND HYPERCHOLESTEROLEMIC RABBITS IN VIVO

The in-vivo low-density lipoprotein (LDL)-uptake by the liver was monitored during the initial 60 minutes after injection of radiolabelled LDL. LDL-uptake by the liver as evidenced by the liver/blood pool ratio in normocholesterolemic male New Zealand white rabbits (44.2 +/- 3.1% of whole body activity) was almost double as compared to the ones fed a 1% cholesterol enriched diet (22.5 +/- 3.3%). The blood disappearance of 125I-LDL was significantly faster in normocholesterolemic animals. A 4-week treatment with the dihydropyridine calcium channel blocker isradipine resulted in a significantly enhanced LDL-binding by the liver, both in normo- and hypercholesterolemic animals to a comparable extent. A concomitant acetylsalicylic acid (ASA) treatment completely abolished the benefit induced by isradipine while ASA alone was ineffective. Similarly, 125I-LDL disappearance from blood was improved by isradipine, while ASA neutralizes this effect. Again, ASA alone did not change the kinetics. Plasma cholesterol and high-density lipoprotein (HDL) cholesterol remained unchanged. Isradipine significantly enhanced vascular prostaglandin(PG)I2-generation while concomitant ASA treatment or ASA application alone almost completely depressed PGI2-formation. It is concluded that the improved LDL-binding by the liver is due to an enhanced PGI2-formation evoked by isradipine.

Passive smoking increases platelet thromboxane

Although active smoking is known to enhance platelet thromboxane production, no data on passive smoking are available yet. In an 18 m3 room, the influence of single and repeated exposure to passive smoke for 60 minutes was assessed in nonsmokers and smokers. Smokers and nonsmokers were matched for sex and age. All the evaluated parameters (plasma TXB2, serum TXB2, malondialdehyde, 11-dehydro-TXB2, conversion of exogenous arachidonic acid to hydroxy-5,8,10-heptadecatrienoic acid, and TXB2) were higher in smokers than nonsmokers at baseline conditions, immediately and 6 hours after passive exposure to cigarette smoke. Repeated exposure of nonsmokers rendered their platelets more activated, so they became closer to the behavior of smokers. Contributing to the development of hemostatic imbalance, these results indicate that passive smoking may enhance thromboxane A2 release from the platelets.

Systematic screening for cardiovascular risk at pharmacies

Background Early identification and treatment of cardiovascular risk factors (CVRFs) is essential to prevent excess morbidity, mortality and healthcare-related costs. We sought to investigate whether an active screening programme at pharmacies could identify a significant proportion of patients with previously undetected CVRFs. Methods and results Between April and July 2013, 184 pharmacies in Lower Austria enrolled a total of 6800 participants, in whom body mass index (BMI), blood pressure (BP), total cholesterol and blood glucose were measured. Mean age was 58±17 years and 67.8% were women. 21% of men and 16% of women had a BMI≥30 kg/m2. The crude prevalence of diabetes mellitus (DM) was 7%, hypercholesterolaemia was identified in 57%, and 44% had elevated BP. Among fasting individuals (n=1814), DM was found in 18%. In total, 30% were confronted with a CVRF they were previously unaware of, and pharmacists recommended 45% of all participants to actively consult a physician. A first-time diagnosis of a CVRF was most frequent in the age groups between 25 and 64 (32% of participants). Conclusions This pharmacy-based approach for cardiovascular risk screening found similar overall prevalences of CVRFs as reported by national surveys, but revealed underdiagnoses, particularly in lower age groups. A previously unknown CVRF was identified in every third individual, frequently prompting the pharmacists to recommend the consultation of a physician. An active screening approach at pharmacies might therefore serve as an effective alternative to the public preventive medical examination, particularly in younger age groups.