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Biomedical subjects

G Stark

Publications and source records attributed to G Stark.

At least 109 records · Page 6Linked to original sources
PubMed1991

Radiation inactivation of ion channels formed by gramicidin A. Protection by lipid double bonds and by alpha-tocopherol.

The conductance induced by the channel-forming peptide gramicidin A in lipid membranes is reduced by many orders of magnitude on exposure of the membrane and its aqueous environment to ionizing radiation. This results from an interaction of free radicals of water radiolysis with the tryptophan residues of gramicidin A. The sensitivity of the ion channels towards irradiation is strongly reduced in the presence of either vitamin E or of highly unsaturated lipids. An increase of the D37 dose up to a factor of 50 was found. The phenomena are interpreted via a reduction of the effective concentration of free radicals (such as OH.) in the membrane by reaction with unsaturated fatty acid residues or with vitamin E.

Electric Conductivity↗
PubMed1991

Acute effects of the ACE inhibitor lisinopril on cardiac electrophysiological parameters of isolated guinea pig hearts.

Angiotensin-converting enzyme (ACE) inhibitors are of benefit in life-threatening ventricular arrhythmias in patients with congestive heart failure and ventricular tachycardia caused by the onset of myocardial ischemia as well as by reperfusion of an ischemic area. The aim of the present study was to investigate whether direct electrophysiological effects are responsible for these observations. Therefore, we investigated the electrophysiological effects of lisinopril on the whole cardiac conduction and pacemaker system in isolated guinea pig hearts perfused by the method of Langendorff at concentrations of 0.01, 0.1, 1, and 10 microM. Lisinopril did not affect heart rate, atrioventricular, His bundle, or intraventricular conduction at any of the concentrations tested. Likewise the frequency-dependent QT duration was unchanged. At a concentration of 10 microM, lisinopril prolonged effective refractory period evaluated by premature beats (46 +/- 15%, n = 8, p less than 0.01) as well as the rate-dependent effective refractory period (31 +/- 12, n = 8, p less than 0.01) of the atrioventricular conduction. These effects can be explained by lisinopril's action as a minor calcium antagonist at a toxic concentration of 10 microM. The present results show that electrophysiological parameters are not substantially altered by lisinopril. Therefore, several other mechanisms such as the unloading of the left ventricle and/or the suppression of noradrenalin release and the electrolyte (potassium and magnesium) repletion and/or regression of left ventricular hypertrophy as long-term effects may play a major role in the antiarrhythmic efficacy of ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

The increase of membrane capacitance as a consequence of radiation-induced lipid peroxidation.

The electrical capacitance of lipid membranes may increase by up to 50% on exposure to ionizing radiation. This is the consequence of lipid peroxidation induced by primary or secondary radicals of water radiolysis in the presence of oxygen. The polar products of this process give rise to an increase of the dielectric constant of the membrane. This in turn leads to the increase of membrane capacitance observed. An important consequence of this phenomenon is the reduction of the inner energy barrier between the two membrane/water interfaces influencing the movement of charged particles across the membrane. Thus the comparatively small change of the dielectric constant gives rise to the large increase in membrane conductance (by up to several orders of magnitude) observed in the presence of macrocyclic ion carriers of the valinomycin type (Strässle et al. 1987b). The results were obtained applying a novel method to measure time-dependent changes of the capacitance of planar lipid membranes.

Dose-Response Relationship, Radiation↗
PubMed1991

Acute effects of amiodarone on ultrastructure and electrical activity of isolated guinea pig hearts.

STUDY OBJECTIVE: The aim was to evaluate the effects of tissue concentration of amiodarone on ultrastructure and electrical activity in isolated spontaneously beating Langendorff perfused guinea pig hearts. DESIGN: Group 1: The influence of 10 microM amiodarone over a period of 1 h in a non-recirculated perfusate on conduction intervals, heart rate, creatine kinase concentration in the coronary effluent, coronary flow, and drug accumulation was determined. Group 2: Ultrastructural changes after 30 min and 60 min perfusion with amiodarone were examined. Group 3: Cardiac refractoriness was evaluated following 30 min and 60 min of perfusion with amiodarone. EXPERIMENTAL PREPARATIONS: Isolated hearts of guinea pigs (200-300 g) were used: group 1, n = 6 animals; group 2, n = 3 for each time span; and group 3, n = 6 for each time span. MEASUREMENTS AND MAIN RESULTS: A steady state for the effects of amiodarone on atrioventricular and intraventricular conduction [+31(SEM 5)%, p less than 0.01% +47(12)%, p less than 0.01, respectively] and on heart rate [-30(9)%, p less than 0.01] was reached after 15 min, and on His bundle conduction [+38(17)%, p less than 0.01] after 30 min. QT duration was not affected throughout the duration of the experiment. Cardiac refractoriness was significantly prolonged following 30 min perfusion with 10 microM amiodarone, and was further significantly increased following 60 min perfusion. Amiodarone tissue concentration increased to 365(39) nmol.g-1 wet weight, and this was accompanied by an increase in creatine kinase concentration in the coronary effluent. Coronary flow stayed constant throughout the whole experiment. At the end of the experiment electron microscopic examination of the myocardium of the left ventricle showed accumulation, fusion, and vacuolisation of mitochondria, and perinuclear oedema. CONCLUSIONS: These observations suggest that amiodarone, as well as exerting acute electrophysiological effects, creates ultrastructural changes which probably contribute to its effectiveness in arrhythmias caused by scarred myocardium.

Amiodarone↗
PubMed1991

Nd:YAG laser with sapphire tip combined with balloon angioplasty in peripheral arterial occlusions. Long-term results.

In 167 patients with complete occlusion (greater than 3 cm) of the femoropopliteal artery, percutaneous transluminal laser angioplasty (PTLA) was performed after an unsuccessful attempt at crossing with a guide wire and was immediately followed by balloon dilatation. An Nd-YAG laser and an optical fiber delivery system with a sapphire tip serving as a contact probe were used for PTLA. In 132 of 167 (79%) patients, the occluded segment was successfully reopened. Clinical symptoms improved in 126 of 167 (75%) patients. PTLA was unsuccessful in 35 patients, and in 15 of these, injury of the vessel wall occurred. In one patient, surgical drainage of a large hematoma became necessary. All patients in whom recanalization had been achieved were randomized to receive long-term treatment with either phenprocumarol or acetylsalicylic acid (ASA) plus dipyridamole to prevent rethrombosis. At 36 months of follow-up, the cumulative patency rate (CPR) was 63%. A complete reobstruction in 32 patients (24%) and a partial reobstruction in 15 patients (11%) were found angiographically. The CPR after 36 months was significantly lower (p less than 0.05) in patients younger than 60 years of age (54%) than in patients older than 60 (68%); it was also significantly lower (p less than 0.05) in patients with reduced peripheral runoff (55%) due to obstructed arteries of the lower leg than in patients with unaffected runoff (73%). The CPR was 65% in recanalized segments shorter than 7 cm and was 62% in recanalized segments longer than 7 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Etiology of deep venous thrombosis of the leg].

50% of all patients with deep venous thrombosis (DVT) are simultaneously suffering from other diseases, which might support or cause the thrombogenesis. In the other 50% no etiological factor can be identified. There are several factors predisposing to DVT, such as immobilisation, surgery, old age of the patient, estrogen treatment. These factors are risk factors but not etiological factors. DVT is not only initiated by the three main factors (hypercoagulability, stasis, endothelial lesion) already described by Virchow. A very complicated balance of several complex single systems (endothelium, vessel wall motion, thrombocytes, hemostatic and fibrinolytic systems with their inhibitors) has to be disturbed in order to initiate venous thrombosis.

Blood Coagulation Factors↗
PubMed1990

4'-O-tetrahydropyranyl-doxorubicin in advanced breast cancer: a phase II study.

In a phase II study, 35 patients with advanced breast cancer were treated with 4'-O-tetrahydropyranyl-doxorubicin (THP-DXR) (70 mg/m2 i.v. on day 1); treatment was repeated every 3 weeks. Eight patients had failed prior chemotherapy for advanced disease. A total of 34 patients were evaluable for response. After a median of 10 treatment courses (range, 3-15), objective tumor response was seen in 59% (20 of 34 patients) (95% confidence limits, 42%-75%). In all, 17 partial remissions and 3 complete remissions were observed; stable disease occurred in 13 patients. The median duration of response was 42+ weeks (range, 21 - 77+ weeks). The dose-limiting side effects were leukopenia (26 patients, WHO grade III-IV) and thrombocytopenia (9 patients, WHO grade II-IV). Nausea/vomiting was experienced by 34 patients; in 18, it reached WHO grade II-III. Other treatment-related side effects included alopecia (WHO grade II-III) in 26 patients and stomatitis and diarrhea (WHO grade I-III) in 9 patients. At cumulative doses of THP-DXR of at least 700 mg/m2 (range, 700-1,050 mg/m2), no signs of congestive heart failure were observed. We conclude that THP-DXR is effective for first- and second-line chemotherapy in advanced breast cancer and that side effects are manageable.

Adult↗
PubMed1990

Comparison of acute effects of anthracyclines on cardiac electrophysiological parameters of isolated guinea-pig hearts.

This study was performed to evaluate the acute effects of two anthracycline derivatives, doxorubicin and 4'O-tetrahydropyranyl-doxorubicin [(THP)-doxorubicin], on the conduction intervals, heart rate and refractoriness of isolated spontaneously beating guinea-pig hearts using a high-resolution ECG recording technique (SST-ECG). Doxorubicin as well as (THP)-doxorubicin were added to the perfusate in increasing concentrations of 0.1, 1 and 10 microM. Doxorubicin did not significantly alter the heart rate or conduction intervals. Only the rate-dependent QT interval was significantly shortened under the influence of 10 microM doxorubicin. In contrast, 10 microM (THP)-doxorubicin led to a significant reduction in the heart rate (-13% +/- 3%; P less than 0.01, n = 7) and to a prolongation of atrioventricular conduction time (24% +/- 10%; P less than 0.05, n = 7). The rate-dependent repolarization period (QT interval) was only insignificantly shortened in the presence of 10 microM (THP)-doxorubicin. The maximal following frequencies of each part of the conduction system were not changed by 10 microM doxorubicin. In the presence of (THP)-doxorubicin, the maximal following frequency of the ventricular myocardium was increased by as much as 36% +/- 8% (P less than 0.01, n = 7), indicating a shortening of the effective refractory period of the ventricular myocardium (V-ERP). These results show that the activation of (THP)-doxorubicin resembles the effects of Ca-antagonistic compounds on the heart (i.e. decrease in the spontaneous sinus rate and prolongation of the AV-nodal conduction interval). Changes in the QT interval exerted by doxorubicin and the shortening of the ventricular effective refractory period by (THP)-doxorubicin may indicate an alteration of the K(+)-conductance of the membrane. As the acute electrophysiological effects of doxorubicin and (THP)-doxorubicin are modest and occur only at excessive concentrations (10 microM), a direct influence on the generation of arrhythmias in healthy hearts is unlikely.

Animals↗
PubMed1990

Patients who initially refuse prehospital evaluation and/or therapy.

The authors performed a retrospective descriptive and analytical cohort study of prehospital patient initial refusal of care (PIRC) cases to characterize the types of patients encountered and to assess factors associated with their dispositions. During a 6-month period, 169 of 1715 (9.9%) base station calls in an urban emergency medical service (EMS) system were for physician involvement in a PIRC. Patients' dispositions were as follows: left at scene against medical advice (53%); taken by ambulance to the hospital (28%); left with friend (13%); other disposition (5%). While police were called to the scene 41 times, they placed a "legal hold" on only 10 patients. Leaving the patient at the scene against medical advice was associated (logistic regression analysis; P less than .05) with the absence of the following factors: family on the scene and a police hold, and with the presence of the following factors: treated hypoglycemia, alcohol use, orientation, and normal speech. The development of statutes that allow police hold placement under the guidance of the base station physician may be necessary. Such statutes would aid transportation of a patient considered by EMS personnel to have impaired mental capacity that may limit the patient's ability to understand medical care decisions.

Cohort Studies↗
PubMed1990

Different stereoselective effects of (R)- and (S)-propafenone: clinical pharmacologic, electrophysiologic, and radioligand binding studies.

Propafenone is a class 1c antiarrhythmic agent with moderate beta-blocking activity as a result of a structural similarity to beta-adrenoceptor antagonists. In a randomized, double-blind crossover exercise study, eight healthy volunteers were examined before and 2 1/2 hours after oral administration of 300 mg (R,S)-, 150 mg (R)-, and 150 mg (S)-propafenone hydrochloride. The mean rate pressure product was significantly reduced by (R,S)-propafenone hydrochloride (-5.2%; p = 0.045) and half-dosed (S)-propafenone hydrochloride (-5.9%; p = 0.013), whereas the (R)-enantiomer caused no significant changes. There was a significant difference between the effects of (R)- and (S)-propafenone (p = 0.033). In beta-adrenoceptor-binding inhibition experiments with (S)-(125I)iodocyanopindolol in a sarcolemma-enriched cardiac membrane preparation, the eudismic ratio of (S)- over (R)-propafenone was 54. On the spontaneously beating Langendorff-perfused guinea pig heart, 3 x 10(-6) mol/L of both (R)- and (S)-propafenone resulted in significant changes (p less than 0.01) on His bundle conduction (+79% +/- 27% and +69% +/- 9%), as well as comparable decreases in the maximal rate of pacing with 1:1 conduction of the atrial (-54% +/- 10% and -57% +/- 8%) and ventricular myocardium (-42% +/- 6% and -43% +/- 6%), indicating equal effects in sodium channel-dependent antiarrhythmic class 1 activity. Thus (R)- and (S)-propafenone exert different beta-blocking actions but equal effects on the sodium channel-dependent antiarrhythmic class 1 activity. More specific antiarrhythmic class 1 therapy with reduction of beta-blocking side effects may be attained with optically pure (R)-propafenone hydrochloride instead of the currently used racemic mixture.

Administration, Oral↗