F. Rauscha

Evaluation of esophageal tracheal combitube in cardiopulmonary resuscitation.

Prompt establishment of an airway is a primary goal in CPR of nonbreathing and unconscious patients. The esophageal tracheal combitube (ETC) is a new airway, designed for emergency intubation providing sufficient ventilation whether the airway is placed into the trachea or into the esophagus. We evaluated the effectiveness of the ETC in 31 patients during CPR. Blood gas analyses obtained during esophageal placement of the ETC showed results comparable to those of ventilation with a conventional endotracheal airway (ETA). The ETC appeared to oxygenate and ventilate patients adequately without complications. The efficacy, safety, and ease of insertion ensure rapid airway control. It is concluded that the ETC provides a sufficient alternative to the ETA whenever ideal conditions or trained staff for endotracheal intubation are not immediately available.

Synergistic effect of prostaglandin E1 and isosorbide dinitrate in peripheral vascular disease

Isosorbide dinitrate, which releases nitric oxide in vivo, and prostaglandin E1 synergised in reducing platelet deposition and increasing platelet survival time in patients with peripheral vascular disease.

Autologous low-density lipoprotein labelling allows characterization of human atherosclerotic lesions in vivo as to presence of foam cells and endothelial coverage

The monitoring of local vascular kinetics after injection of autologous radiolabelled low-density lipoprotein (LDL) allows characterization of human atherosclerotic lesions as to the presence of foam cells and the quality of endothelial coverage. The following evidence exists: (1) dynamic imaging reveals two types of visual LDL accumulation in the vascular bed, one increasing, becoming visible sometimes only as late as after 24 h, and the other one appearing very early on, but decreasing with time; (2) the accumulation of iodine-123 LDL or iodine-131 LDL in the vascular bed shows three major types of local kinetic curves, which correlate with scintigraphic findings; (3) the accumulation of radiolabelled LDL in the vascular bed of humans in vivo is similar to its uptake in de- and re-endothelialized vessels of experimental animals using 125I-LDL; (4) morphological control in endarteriectomy samples confirms the hypothesis that this promising new approach may for the first time allow the in vivo monitoring of preclinical lesions in humans.

Acute chest pain*/a stepwise approach, the challenge of the correct clinical diagnosis

STUDY OBJECTIVE To assess the safety and the accuracy of a 4 h stepwise diagnostic approach relying on clinical judgement in unselected patients with acute chest pain. DESIGN Prospective cohort study. SETTING Emergency department (ED) of a tertiary care university hospital. PATIENTS 1288 unselected patients presenting with acute chest pain. INTERVENTIONS After history and physical examination, clinical judgement (step I), governed the need for further patient evaluation: baseline 12 lead electrocardiogramm (ECG) and laboratory examinations (step II), serial 12 lead ECG and laboratory examinations after 4 h (step III), and 4 h troponin T measurement (step IV) to exclude or to confirm a coronary origin of chest pain. Patients were followed clinically for 6 months for future occurrence of cardiac events (myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), CABG, cardiac death), any death and for accuracy of the ED diagnosis in non-coronary chest pain patients. MEASUREMENTS AND RESULTS Chest pain was diagnosed to be coronary in origin in 381 and non-coronary in 907 patients, respectively. Cardiac events occurred during follow up in 240 (19%) of 1288 patients, in 233 of 381 (61%) with presumed coronary and seven of 907 (1%) with presumed non-coronary chest pain. Sensitivity, specificity, positive predictive value and negative predictive value for correct detection of coronary chest pain were 97, 86, 61 and 99%, respectively. In non-coronary chest pain patients the agreement between the ED diagnosis and the final diagnosis was good (kappa=0.71, 95% confidence interval (CI) 0.67-0.75). CONCLUSIONS The 4 h stepwise approach guided by clinical judgement was safe for ruling out impending cardiac events in unselected patients with acute chest pain. However, more extensive evaluation is necessary for accurate rule-in of coronary chest pain.

Comparable effect of prostaglandin E1 in decreasing in vivo platelet deposition on human lesion sites after intravenous and intraarterial application

It had been claimed that prostaglandin E1 is degraded during first lung passage to a major extent. Clinical results, however, as well as various platelet function tests and coagulation parameters revealed no apparent difference after i.v. and i.a. infusion. Thus, we examined the question what the quantitative difference between i.v. and i.a. PGE1-application would be upon in-vivo platelet function assessed by platelet uptake over active lesion sites as well as platelet half-life monitoring after autologous 111-In-oxine platelet labelling. In patients suffering from peripheral vascular disease stage II according to Fontaine PGE1 was able to decrease platelet uptake after i.v. and i.a. therapy to a comparable extent; similarily, a significant prolongation in platelet half-life was noted, again revealing no difference. As the decrease in platelet uptake is assumed to be predominantly a vascular effect, it is hypothetized that more stable derivatives of PGE1 are active, counterbalancing a lower biological activity with a longer half-life.

Modification of platelet function by isosorbide dinitrate in patients with coronary artery disease

The effect of a four weeks oral treatment with 100 mg isosorbide dinitrate (ISDN) daily on platelet function was evaluated in 40 patients (aged 40-65 years) with proven coronary artery disease. Isosorbide dinitrate decreased platelet reactivity to ADP (p less than 0.001), increased platelet sensitivity to PGI2 (p less than 0.01) while the production of TXB2 from exogenous arachidonic acid substrate and from endogenous substrate were both significantly reduced. Circulating platelet aggregates as measured by the Wu-test were markedly reduced (p less than 0.001) but there was little change in the plasma concentration of the platelet proteins beta-thromboglobulin and platelet factor 4. Overall, platelet activation correlated with smoking, hypertension and a family history of coronary artery disease. The reduced platelet activation seen during treatment with isosorbide dinitrate may contribute to the therapeutic benefit seen with this drug in patients with coronary artery disease.

Acute chest pain--identification of patients at low risk for coronary events. The impact of symptoms, medical history and risk factors.

ZusammenfassungStudienhintergrundDie Evaluierung von Patienten mit akutem Thoraxschmerz bleibt schwierig und mit dem Risiko einer gravierenden Fehldiagnose verbunden. Es ist bekannt, dass typische Angina pectoris-Symptomatik koronare Hochrisiko-Patienten nicht sicher identifiziert. Wir untersuchten den Vorhersagewert von atypischen Charakteristika, mit Bezug auf akute Symptomatik, Anamnese und Risikofaktoren der Patienten, für den Ausschluss von akutem Myokardinfarkt oder sub-akuten koronaren Ereignissen.Methoden1288 konsekutive Patienten mit akutem Thoraxschmerz wurden an einer Notaufnahme untersucht. Symptome, Anamnese und Risikofaktoren wurden unter Verwendung von 7 prä-definierten Kriterien evaluiert und als typisch oder atypisch für Myokardischämie eingeteilt. Der positive Vorhersagewert (PPV) und 95% Konfidenzintervalle (95% Cl) wurden berechnet, um akuten Myokardinfarkt (AMI), und kardiale Komplikationen (MACE: kardiovaskulärer Tod, perkutane Angioplastie, Bypass Chirurgie, Myokardinfarkt) innerhalb von 6 Monaten vorherzusagen oder auszuschließen.ErgebnisseAMI wurde in 168 Patienten (13%) gefunden, und 6-Monate MACE (inklusive AMI) in 240 Patienten (19%). Bei Vorhandensein von ≥4 typischen Kriterien konnte AMI mit einem PPV von 0,21 (0,17 bis 0,25) vorhergesagt werden, und 6-Monate MACE mit einem PPV von 0,30 (0,25 bis 0,35). Das Vorhandensein von ≥4 atypischen Kriterien hingegen war mit einem PPV von 0,94 (0,91 bis 0,96) zum Ausschluss von AMI, und mit einem PPV von 0,93 (0,90 bis 0,96) zum Ausschluss von 6 Monate MACE verbunden. In 165 von 476 Patienten unter 40 Jahren (35%), waren AMI bzw. 6-Monate MACE bei ≥4 atypischen Kriterien mit PPVs von 0,98 (0,96 bis 1,0) auszuschließen.SchlussfolgerungDie Evaluierung von für eine Myokardischämie atypischen Kriterien kann bei der Identifikation von Patienten mit niedrigem Risiko hilfreich sein, während typische Kriterien nur einen eingeschränkten diagnostischen Wert besitzen.SummaryBackgroundThe evaluation of patients with acute chest pain remains challenging, as it implies the risk of fatal misdiagnosis. It is well recognized that typical angina does not specifically identify patients at high risk. we investigated the predictive value of characteristics atypical for myocardial ischemia for exclusion of acute or subacute coronary events, focusing on patients’ symptoms, medical history and risk factors.MethodsWe prospectively studied 1288 consecutive patients presenting with acute chest pain at a nontrauma emergency department. Patients’ symptoms, history and risk factors were evaluated using seven predefined criteria and assigned as typical or atypical for ischemic coronary chest pain. Positive predictive value (PPV) and 95% confidence intervals (95% Cl) were calculated to predict or exclude acute myocardial infarction (AMI) and major adverse cardiac events (MACE: cardiovascular death, percutaneous coronary interventions, bypass surgery, or myocardial infarction) within six months.ResultsAMI occurred in 168 patients (13%), and 6-months MACE (including AMI) overall in 240 patients (19%). Presence of four or more criteria typical for myocardial ischemia was associated with a PPV of 0.21 (0.17 to 0.25) for predicting AMI and 0.30 (0.25 to 0.35) for 6-months MACE. Presence of four or more criteria atypical for coronary ischemia was associated with a PPV of 0.94 (0.91 to 0.96) for excluding AMI and 0.93 (0.90 to 0.96) for excluding 6-months MACE. In 165 of 476 patients under 40 years of age (35%), four or more atypical criteria excluded AMI and 6-months MACE with PPVs of 0.98 (0.96 to 1.0).ConclusionEvaluation of criteria atypical for myocardial ischemia with acute chest pain may help to identify candidates for early discharge, whereas typical characteristics have very little diagnostic value.

Ticlopidine and platelet function in healthy volunteers

The influence of a 4-weeks therapy with 500 mg ticlopidine daily on platelet function parameters was examined in 10 male healthy volunteers aged 20-33 years in order to extend the knowledge on the antiplatelet activity of this substance. Ticlopidine significantly (p less than 0.01) affected ex-vivo platelet aggregation induced by ADP and increased platelet sensitivity to the antiaggregatory action of PGI2. Generation of TXB2 from endogenous substrate during spontaneous clotting of blood (serum-TXB2), conversion of exogenous radiolabelled arachidonic acid into TXB2 and MDA-formation in isolated platelets were unaffected by the treatment. The TXB2-level in plasma of volunteers, however, was decreased, after administration of the drug. The diminished alpha-granule content liberation (beta-thromboglobulin: p less than 0.01; PDGF: p less than 0.01; PF4 not significant) indicates that ticlopidine induces a decrease in platelet activity. The beneficial effect on release reaction is not associated with a decrease in TXA2-formation. Our results demonstrate that ticlopidine inhibits platelet activity, especially the PDGF-release. These results confirm the value of this drug in the prevention of atherosclerosis and its thromboembolic complications.

The diminished extracellular matrix production induced by isradipine, a calcium channel blocker, is completely abolished by cyclooxygenase inhibition

Collagen and glycosaminoglycan synthesis are well known to be enhanced during early atherogenesis. In this experimental study the synthesis of collagen was determined using 14C proline incorporation, the glycosaminoglycan production by means of 35S-sulphate incorporation and subsequent quantification by means of autoradiography. Isradipine, a new calcium channel blocker of the dihydropyridine family at a dose of 0.3 mg/kg significantly (p less than 0.01) decreased the incorporation of both the radioactive precursors. This effect was abolished by a concomitant aspirin treatment, while aspirin alone did not exert any significant effect on the precursor incorporation. These data suggest that isradipine, which is known to stimulate PGI2 synthesis, may exert this antiatherosclerotic inhibitory action on extracellular matrix production via the endogenous liberation of PGI2.

Isradipine inhibits mitotic and proliferative activity in the arterial wall

The anti-mitotic (3H-thymidine uptake quantified using autoradiography) and anti-proliferative (counting of activated smooth muscle cells on semithin sections) effects of the dihydropyridine calcium channel blocker isradipine (0.3 mg/kg) have been assessed in a rabbit arterial stress model. Isradipine caused a significant drop in both mitotic and proliferative activity. These effects were more pronounced by pretreatment (6 hours before lesion induction with desoxycorticosterone) with isradipine as compared to posttreatment (6 hours after experimental lesioning). The benefit induced by isradipine was abolished by aspirin treatment. In-vitro vascular prostacyclin formation and cholesterol content were not affected. These findings suggest that the anti-atherosclerotic action of isradipine on mitotic activity and cellular proliferation is mediated by a cyclooxygenase product, most likely via enhanced local vascular PGI2-synthesis.