[Is patient education using audiovisual methods helpful?]. / Ist Patientenaufklärung mit audiovisuellen Methoden sinnvoll?

In a prospective randomized study we compared the effectiveness of preparatory information with and without a video film show about a planned heart catheterization. 65 patients were included, 5 were later excluded for medical reasons. One group (n = 34) received preparatory disclosure from a standard pamphlet and a personal interview; the other group additionally watched a 14 min video (n = 26). Only the latter group had a significant reduction of anxiety scores. Patients said they received better information from the film than from the pamphlet. Duration of the personal interview did not differ. Viewing the video may improve patient compliance.

Effect of serotonergic antagonism on local responses to an acute and selective endothelial trauma in vivo.

Serotonin is liberated during platelet release reaction. It is concluded from in vitro experiments that serotonin influences both platelet activation and thrombus-induced vasoconstriction. The subject of the present study was to assess the impact of the serotonin2 antagonist naftidrofuryl on both thrombogenesis and thrombus-induced vasoconstriction in vivo. In a hamster cheek pouch, vessels form a rich meshwork, allowing repetitive experiments to obtain intraindividual control measurements. With a contactless photochemical process, endothelial cells can be damaged in vivo. Regularly platelets and the coagulation system are activated and thrombi are formed. In larger arterial vessels local vasoconstriction occurs. Thrombogenesis was induced in arterioles with an inner diameter between 17 and 20 microns. It was monitored by the continuous measurement of blood cell velocity to assess initial hemodynamics and the interval elapsing until perfusion stops. Solvent alone had no effect. Naftidrofuryl was given in clinically relevant dosages of 1, 5, and 20 mg/kg intra-arterially. Even 1 mg/kg showed a significant antithrombotic effect. Efficacy increased in a dose-related manner as well as during the time interval of observation (i.e., 2 h after application). As an established antithrombotic standard, acetylsalicylic acid was applied in dosages of 10 and 100 mg/kg. Both dosages were found to be antithrombotic, but not more effective than comparable dosages of naftidrofuryl. Larger arterioles with an inner diameter of about 50 microns have smooth muscle cells. They constrict during thrombogenesis as a local response to substances released by the thrombus. Topical application of papaverine abolished vasoconstriction. A thromboxane antagonist (EP092) was also effective. Naftidrofuryl reduced the vasoconstriction whereas its solvent was without effect.

[Acute myocardial infarct caused by nicotine-induced erythrocytosis]. / Akuter Myokardinfarkt bei durch Nikotinabusus induzieter Erythrozytose.

A 29-year-old heavy smoker presented with an acute myocardial infarction and hematocrit of 70%. At immediate coronary angiography a complete occlusion of the right coronary artery was found. After intracoronary urokinase the coronary arteries were found to be completely normal. Causes for the erythrocytosis other than smoking could be excluded. We conclude that thrombotic coronary occlusion with acute myocardial infarction was caused by erythrocytosis due to heavy smoking.

Single-bolus injection of recombinant tissue-type plasminogen activator in acute myocardial infarction.

Recombinant tissue-type plasminogen activator (rt-PA) has hitherto been administered in acute myocardial infarction as an intravenous infusion with an initial bolus of about 10% of the total dose, both due to its short half-life and to avoid possible early reocclusions. A single-bolus dose would simplify the therapeutic regimen. Therefore, 20 patients with symptom duration of 125 +/- 58 minutes were given a single bolus of 50 mg of rt-PA over 2 minutes. Coronary angiography 60 minutes after the rt-PA bolus revealed a patent infarct-related artery in 15 of 20 patients (patency rate 75%, 95% confidence limits 51 to 91%). In the remaining patients, reperfusion was achieved by coronary angioplasty and intracoronary fibrinolysis; in 2 patients coronary artery bypass grafting was necessary. Control angiograms at 24 hours showed reocclusions in 4 of 18 patients. One woman died due to an intracranial hemorrhage 48 hours after the rt-PA bolus injection. Circulating fibrinogen decreased from 2.7 +/- 0.5 to 1.5 +/- 0.9 g/liter after 2 to 4 hours and reached the initial value within 24 hours. Pharmacokinetic parameters were obtained in 7 patients by measuring rt-PA antigen levels in multiple plasma samples. Mean peak rt-PA concentration was 9.8 +/- 3.6 micrograms/ml, total plasma clearance 476 +/- 148 ml/min and dominant half-life 4.8 +/- 1.0 minutes. Thus, rt-PA administered as a 50-mg single bolus appears to provide similar patency rates and shows similar kinetics in comparison with the conventional infusion regimen. Assessment of the incidence of bleeding complications requires further studies.

A randomized prospective study on anxiety reduction by preparatory disclosure with and without video film show about a planned heart catheterization.

Unfortunately, giving preparatory information to the patient is generally regarded as legally mandatory for obtaining his written consent to an invasive procedure. Disclosure, however, could be used to reduce his anxiety as well; we hypothesized that showing a preparatory video film might be helpful in this respect. Patients who were admitted for elective coronary angiography were eligible for the study. 65 were randomized to two groups: both groups received the same leaflet and personal interview with the doctor, but only one group (Group 2) additionally watched a 14 min preparatory video. Anxiety was assessed with the State-Trait Anxiety Inventory (STAI). The two groups did not differ with respect to initial anxiety levels and other important parameters. Group 1 patients, who did not watch the video had no significant reduction in anxiety score; group 2 patients showed a significant benefit. We conclude that disclosure with the additional aid of a video film may be an easy, yet effective way to reduce patients' anxiety.

[The dose of intracoronary urokinase infusion in acute myocardial infarct]. / Dosierung der intrakoronaren Urokinase-Infusion beim akuten Myokardinfarkt.

In 11 patients with acute myocardial infarction (mean age 52 +/- 6 years) coronary angiography was performed 4.5 +/- 3.6 h after the onset of symptoms. The infarct-related artery was in 7 cases the right coronary artery and in 4 cases the left anterior descending branch of the left coronary artery. The infarct-related artery showed total or subtotal occlusion and no perfusion (Thrombolysis in Myocardial Infarction trial (TIMI) grade 0 or 1). In 7 cases Urokinase was infused intracoronarily at a dosage of 250,000 IU over 30 min, but in only 1 case partial reperfusion was achieved. However, all patients treated with 500,000 IU Urokinase over 30 min or 1 Mill IU over 60 min had successful reperfusion (TIMI grade 2 or 3). Thus, it appears that 500,000 IU up to 1 Mill IU of Urokinase over a period of 30 to 60 min is adequate for intracoronary thrombolysis in patients with acute myocardial infarction.

[Observation of acenocoumarol-induced granulocytosis]. / Beobachtung einer Acenocoumarol induzierten Granulocytose.

A male patient had been treated with acenocoumarol for 9 years. Raised white cell count returned to normal, when acenocoumarol was substituted by heparin, but rose again after reexposure. An analysis of variance showed that this effect is mediated by neutrophils only. The rise is quick and may therefore be caused by a redistribution of white cells rather than by increased cell production.

Local measurements of thrombus induced vasoconstriction in vivo.

No data is available describing the local effect of thrombus formation on the vessel's diameter in vivo. As platelet or thrombus induced vasoconstriction seems to be of clinical importance in various diseases, it is desirable to get insight into the interrelation of thrombus formation and local vasoactivity. With a contactless photochemical process, endothelial cells can be damaged and thrombogenesis may be initiated in vivo. After first platelets stick to endothelial cells, a strong vasoconstriction is observed in arterioles. In venules, no vascular reaction can be observed. Constriction is most pronounced at the site of thrombus formation and decreases at growing distance. The thrombus is squeezed by the vascular constriction and thus mechanically held in place and squeezed out. A slight relaxation follows 30-80 min later, but the vessel remains constricted during the following three hours. Thrombus induced vasoconstrictions can be reduced by papaverine, EP 092 (a thromboxane A2 antagonist) and phentolamine in dose-dependent manner in vivo. Papaverine was most effective followed by EP 092, Phentolamine was less effective, showing the minor importance of alpha-receptor stimulation in this model.

Precision velocimetry with digital cross-correlation for flow measurements during thrombus growth.

A precise velocimetry with good frequency response is an indispensable prerequisite to studying hemodynamic effects. The need to monitor minute changes of velocity prompted the development of a software-driven velocimeter that uses a laboratory computer without implementation of specialized arithmetic hardware. Without an on-line output, this setup offers high precision (6000 time shifts), extension of the measuring range to lower velocities by nearly two orders of magnitude, an excellent temporal resolution, and resistance to bad signal-to-noise ratios. The system is described and its characteristic parameters are demonstrated. Velocimetry was performed during experiments on thrombogenesis with and without pretreatment with antithrombotic agents and was found to be valuable in assessing thrombus growth and thrombus stability in vivo.

Influence of heparin, aspirin, streptokinase and factor VIII (AHF) on amorphous electron-dense substance, a mediator of platelet and thrombus adhesion in vivo.

Platelet adherence and aggregation on vessel walls are the first crucial steps in thrombogenesis and atherosclerosis. Whether platelets can be activated on damaged endothelial cells or their activation is achieved only when subendothelial structures are exposed was controversially discussed in the past. Recently, an electron-microscopic study has revealed an amorphous electron-dense substance (AEDS) after endothelial cell damage and has discussed its role as a possible trigger of thrombogenesis. The aim of the present study is to elucidate the role and origin of this substance and to investigate the influence which inhibitors of platelet function (acetylsalicylic acid), coagulation (heparin), stimulation of fibrinolysis (streptokinase) and addition of factor VIII (AHF) have on AEDS.

Antithrombotic efficacy and its time course after application of naftidrofuryl in vivo.

The antithrombotic efficacy of naftidrofuryl (Naf) was assessed with the following method: an endothelial cell damage is induced in arteriolar vessels of the hamster cheek pouch by intravascular excitation of fluorescein-isothiocyanate-dextran. On these damaged cells, platelets adhere and a stable thrombus grows. This process progressively obstructs the vessel's aperture and hence reduces blood flow. Blood cell velocity may thus be used to quantitate thrombus growth. Thrombus growth is assessed before and repetitively after parenteral application of 1, 5 and 20 mg/kg Naf. Efficacy is compared with 10 and 100 mg/kg acetylsalicylic acid. Naf shows a significant antithrombotic property, beginning with a dosage of 1 mg/kg which further increases relative to the dosage, and the stability of thrombi decreased. The antithrombotic effectiveness of Naf increases continuously during 120 min after application. Vessel diameter and cell velocity were the same in compared groups thus excluding an influence of the vasodilatory property of Naf on thrombus growth. Sixty min after application, 5 mg/kg Naf was as effective as 10 mg/kg acetylsalicylic acid.

Lipoxygenase products: leukotrienes C4, D4, A4's breakdown products and 12-HPETE influence platelet aggregation in vivo.

Clinical and pathological observations of diseases concomitant which leukotriene release show consistently an involvement of platelet activation. This effect was hitherto believed to be due to tissue trauma. The aim of the present study was to elucidate whether lipoxygenase products such as leukotrienes C4, D4, 12-HPETE and the breakdown products of leukotriene A4 have a direct pro-aggregatory property of their own. Platelet aggregation was induced by intravascular excitation of fluoresceiniso-thiocyanate-dextran in arterioles of the hamster cheek pouch. "Time to aggregate appearance" was assessed prior and after parenteral application of the studied compounds. LTA4's breakdown products were found to have anti-aggregatory properties, whereas LTC4, D4 and 12-HPETE enhanced platelet aggregability.

Ultrastructural observations of an electron dense amorphous layer on selectively damaged endothelial cells, a possible trigger of thrombogenesis in vivo, and its inhibition by nafazatrom.

Platelet aggregation can be induced by intravascular excitation of fluoresceinisothiocyanate-dextran. Cheek pouches of untreated hamsters and of nafazatrom recipients were excised before and after exposure to the exciting light for 1, 4, 6, 10 and 25 minutes and examined electron microscopically. The first observable ultrastructural change was a swelling of endothelial cells. Polymorphonuclear leukocytes began to transmigrate into the interstitium. After 4 minutes, amorphous, optically dense substances appeared on endothelial surfaces. Only on these which platelets later became adherent. Thrombi grew until vessels were occluded. The thrombi were formed by the amorphous structure, degranulated platelets and unaffected red blood cells and leukocytes. No fibrin strands were observed. Pretreatment with 100 micrograms/kg b.w. nafazatrom, a potent antithrombotic agent which stimulates endothelial release of prostacyclin, totally abolished the occurrence of the observed amorphous epiendothelial structure as well as the occurrence of platelet thrombi.

Antiaggregatory efficacy and its time-course after application of acetylsalicylic acid, prostacyclin and nafazatrom in vivo.

Antiaggregatory potency and time courses of their respective efficacy were assessed for acetylsalicylic acid, prostaglandin (PGI2) and nafazatrom, a stimulator of PGI2-release from endothelial cells, and were compared in vivo. Endothelial cell damage was induced by excitation of intravascular fluoresceinisothio-cycanate-dextran. Time from onset of the noxious stimulus to aggregate appearance (TAA) was assessed and dose-dependently delayed by antithrombotic compounds. PGI2 was two orders of magnitude more effective than nafazatrom, acetylsalicylic acid was three orders of magnitude less effective than nafazatrom. Whereas the antiaggregatory potency of PGI2 decreased after 3.1 min to 50%, the antithrombotic efficacy of both, ASA and nafazatrom, further increased after a single bolus injection.

Platelet aggregation in arterioles of the hamster cheek pouch and in heart transplants: its tissue-dependent influencibility by acetylsalicylic acid and nafazatrom.

Different, tissue-dependent antiaggregatory properties of endothelial cells are suggested by in vitro findings, which show different spectra and amounts of arachidonic acid products to be synthesized by vessels of different type and origin. Platelet aggregation was assessed in vivo in native arterioles of the hamster cheek pouch and in arterioles of heart transplants by intravascular excitation of fluorescein isothiocyanate-dextran (FITC-d). The time to aggregate appearance (TAA) was determined, i.e. the interval from onset of FITC-d excitation until the first aggregate was seen to adhere to the vessel wall. Two groups were pretreated with 100 micrograms/kg nafazatrom and 100 mg/kg acetylsalicylic acid (ASA), both potent antithrombotic drugs. Nafazatrom has been shown to stimulate prostacyclin release from endothelial cells, whereas ASA blocks cyclooxygenase both in platelets and vessel walls. TAA was the same for native arterioles of both types. Nafazatrom was equally effective in both vessels, and about three orders of magnitude more potent than ASA in prolonging TAA. ASA was twice as effective in arterioles of the heart as it was in those of the skin type, indicating that tissue-dependent mechanisms achieve the antiaggregatory potency of the vessel walls. It is concluded that further in vivo studies on platelet aggregation and thrombus formation should be performed on cardiac vessels directly and not on vessels of different origin. The presented model may be a useful tool for investigating the mentioned tissue-dependent mechanisms of thrombus formation in vivo.

Platelet aggregation induced in the hamster cheek pouch by a photochemical process with excited fluorescein isothiocyanate-dextran.

Excitation of intravascular fluorescein isothiocyanate (FITC)-dextran by light induces platelet aggregation in arterioles of the hamster cheek pouch. Time to aggregate appearance (TAA) was found to be 45 +/- 5.6 sec in vessels of 10-14 micron diameter. The interindividual differences of TAA are low (coefficient of variance = 12.5%) and the TAA in individual animals can be reproduced for several hours with a coefficient of variance of 14.5%. TAA decreased at higher concentrations of intravascular FITC-dextran (r = 0.98) and with increased energy of the exciting beam. Scavengers of singlet oxygen, sodium azide, and trans-beta-carotene, delayed TAA. A scavenger of hydroxyl radicals, dimethyl sulfoxide, did not influence TAA. Acetylsalicylic acid showed a dose-dependent inhibitory effect from 1 (P less than 0.01) to 100 mg/kg body weight ia. The time-dependent increase of TAA after administration of 100 mg/kg acetylsalicylic acid is demonstrated; the dosage finally delayed TAA to longer than 360 seconds. The findings suggest that platelet formation, initiated by exciting FITC-dextran may involve local production of singlet oxygen. The consequently observed damaging process and the primary role of the endothelial cell damage are described. It is postulated that the described procedure provides a new model of intravascular platelet aggregation, characterized by a good reproducibility. A new damaging mechanism is proposed to study platelet aggregation in vivo.

Vasoconstrictor response of arterioles of the hamster cheek pouch to norepinephrine, prostaglandin H2, F2 alpha and carbocyclic thromboxane A2, a possible thromboxane A2 analogue.

Activated platelets produce thromboxane A2, a potent vasoconstrictor, which may play an important role in pathophysiological disturbances of microcirculation. Thromboxane A2 has a very short half life and has neither been isolated nor synthesized. Hence, the recently reported stable analogue, carbocyclic thromboxane A2 (CTA2), may become an interesting tool in pharmacological research. Its vasoconstrictor potency was compared in vivo with norepinephrine, prostaglandin H2 and F2 alpha using the following method: vessels of a hamster cheek pouch preparation were exposed to a superfusion to which the respective compounds were added to give 1 ng/ml to 0.1 mg/ml final concentrations. The decrease of vessel diameters was measured microscopically. Prostaglandin H2 was found to be the most potent vasoconstrictor followed by CTA2 and norepinephrine. Prostaglandin F2 alpha was least effective. The respective maximal vasoconstrictory responses did not differ significantly.