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Biomedical subjects

E Pilger

Publications and source records attributed to E Pilger.

120 records · Page 7Linked to original sources
PubMed1979

[Effect of biguanids on the lactate metabolism. Studies in diabetics under submaximal ergometric exercise (author's transl)].

24 diabetics without any complications were subjected to an exercise test before and after biguanid therapy. The schedule of the physical strain was a modification of the Kaltenbach diagram. Changes of lactate, pyruvate, pH-standard bicarbonate and base excess values were analysed. Additionally to antidiabetical therapy each of the 8 patients was given either metformin or buformin or phenformin now. Each one of the biguanid derivates induced a rise of the lactate level before and after the exercise test. Phenformin showed the greatest influence on the lactate metabolism, metformin the smallest. Reasons causing the lactogene effect and the quantitative differences of the biguanides are discussed.

Biguanides↗
PubMed1978

[Effect of biguanide therapy on lactate metabolism during graded submaximal ergometric testing].

Diabetic patients were subjected to exercise testing before and after a short antidiabetic therapy with phenformin, buformin or metformin. Primarily, changes of lactate and of the acid base balance, were analyzed. After therapy with biguanides all 24 patients had increased lactate levels before and after physical strain. Phenformin showed the greatest influence on the lactate metabolism. Metformin the least.

Biguanides↗
PubMedDate not supplied

Extended infusion of rtPA lysis of pulmonary emboli: influence of time after onset of symptoms on outcome.

PURPOSE: Evaluate efficacy and safety of short-term thrombolysis with recombinant human-tissue plasminogen activator (rtPA). METHODS: Thrombolysis with rtPA was performed in 29 patients with angiographically documented severe acute pulmonary embolism (Miller score of 20/34 or more). All patients received 100 mg rtPA through peripheral veins within the first 2 hr, followed by a continuous infusion of rtPA (0.05 mg/kg/hr) over a 4-hr period. Concomitant intravenous heparin 1000 U/hr infusion was applicated for the first 6 hr. RESULTS: Using this treatment, 83% of our patients showed clinical improvement objectified by the Miller score, by the clinical stage (Grosser), and by the pulmonary artery mean pressure (PAPm). The treatment regimen was unsuccessful if the clinical history lasted more than 3 days. Complications occurred in 10 patients (34%), and 3 patients (10%) died of acute right heart failure. CONCLUSION: The success of rtPA treatment appears to depend on the interval between onset of symptoms and start of thrombolytic therapy. Otherwise the technique leads to objectifiable improvement within 6 hr with an acceptable bleeding risk.

Adult↗
PubMedDate not supplied

Effects of adenosine on electrical activity of isolated guinea pig hearts.

Negative chronotropic and dromotropic effects of adenosine seem to be responsible for its antiarrhythmic action on supraventricular tachyarrhythmias. To further characterize the effects of adenosine on supraventricular arrhythmias heart rate, conduction, refractoriness, the time to steady-state of AV-nodal conduction slowing and of sinus rate reduction were evaluated. Changes of heart rate, conduction intervals and effective refractory periods were determined by the use of a high-resolution ECG recording technique in isolated guinea pig hearts perfused by the method of Langendorff. Adenosine in concentrations of 3 and 10 microM reduced sinus rate and prolonged AV-nodal conduction significantly, while intraventricular and His bundle conduction were not altered. The maximal effect of adenosine on the sinus node and AV nodal conduction occurred after 636 +/- 109 and 111 +/- 35 (mean +/- SE) beats, respectively. During programmed stimulation at a cycle length of 250 ms, adenosine reduced atrial ERP in a dose-dependent manner. At cycle lengths of 170 and 200 ms, adenosine increased the atrial ERP at 3 microM, and then progressively shortened the ERP at higher doses. At all adenosine concentrations used, the usual rate-dependent adaption in ERP was suppressed. These observations explain the efficacy of adenosine against supraventricular tachyarrhythmias where the AV-node forms a part of a reentrant circuit. Adenosine shortened the atrial ERP, but at high pacing rates also led to a relative prolongation of the atrial ERP as the rate-dependent adaption was suppressed. These opposite effects of adenosine may explain earlier contradictory findings of its action on atrial arrhythmias.

Adenosine↗
PubMedDate not supplied

Stereoselective electrophysiological effects of propafenone in Langendorff perfused guinea pig hearts.

The present study was focused on the stereoselective electrophysiological effects of (R)- and (S)-propafenone.HCl evaluated in isolated Langendorff perfused guinea pig hearts. Conduction intervals were measured using an ECG-recording method of high resolution. Refractory periods of the different parts of the myocardium were determined by stimulation with premature stimuli, as well as by stimulation with increasing pacing rate (rate-dependent/refractory periods). Drug concentrations of 0.1, 1 and 3 microM were tested. Both compounds induced a dose-dependent increase in AV-nodal, His-bundle, and intraventricular conduction time which reached significance (p less than 0.01) following 3 microM of either compound. Sinus rate was also dose-dependently and significantly reduced. (R)- and (S)-propafenone.HCl induced a marked prolongation of the rate-dependent refractory period of sino-atrial (by 140 +/- 22%, p less than 0.01 and by 141 +/- 14%, p less than 0.01, respectively) and AV-nodal (by 34 +/- 22%, p less than 0.01 and by 42 +/- 15%, p less than 0.01, respectively) conduction and of the atrial (by 182 +/- 21%, p less than 0.01 and by 195 +/- 15%, p less than 0.01, respectively) and ventricular (by 93 +/- 16%, p less than 0.01 and by 88 +/- 16%, p less than 0.01, respectively) myocardium. The effective refractory periods evaluated by stimulation with premature stimuli were also significantly prolonged under the influence of (R)- and (S)-propafenone.HCl, except the ventricular myocardial refractoriness by (R)-propafenone.HCl (increase to 114 +/- 23%, n.s.). Both compounds showed a strong rate-dependence of their effects and, thus, the refractory periods evaluated by stimulation with increasing pacing rate were significantly more prolonged than the refractory periods evaluated by stimulation with premature stimuli. The main difference between the effects of (R)- and (S)-propafenone.HCl on the cardiac electrical activity is the lack of effect of (R)-propafenone.HCl on the ventricular myocardial refractoriness evaluated by stimulation with premature stimuli.

Animals↗
PubMedDate not supplied

The effects of the propranolol enantiomers on the intracardiac electrophysiological activities of Langendorff perfused hearts.

The optical isomers of the beta blocking agent propranolol exert beta receptor blocking as well as membrane stabilizing effects. The latter is thought to be responsible for the antiarrhythmic effect of the drug. In this study we quantified the electrophysiological effects of both isomers of propranolol on the conduction and pacemaker system of the heart. The experiments were performed on isolated hearts using a special ECG recording and stimulation technique. To abolish isoproterenol's beta adrenergic stimulatory effect on heart rate, 30-times higher concentrations of (+)propranolol were necessary than of (-)propranolol in order to be consistent. Both isomers caused a similar and marked slowing of conduction velocity through the bundle of His and ventricular myocardium. Also, heart rate, as well as atrio-ventricular conduction velocity were significantly slowed by a concentration of 10 microM of either drug, (-)propranolol being slightly more effective. Only in the presence of (-)propranolol did significant changes of atrio-ventricular and His-bundle conduction occur at a concentration of 1 microM. During programmed stimulation sinus node recovery time was more prolonged by (-)propranolol than during perfusion with (+)propranolol. The highest rate of pacing with 1:1 conduction of the sino-atrial conduction, the atrial and ventricular myocardium was significantly depressed to a comparable degree by either isomers of propranolol. These effects appear to be primarily responsible for the antiarrhythmic effects of both isomers. Because of the minor effects of (+)propranolol on sinus- and AV-node activity, as well as on beta adrenergic receptors, this isomer may have potential clinical importance in the treatment of arrhythmias.

Animals↗
PubMedDate not supplied

Comparison of acute electrophysiological effects of amiodarone and its metabolite desethylamiodarone in Langendorff perfused guinea pig hearts.

During long-term treatment with amiodarone, slowing of conduction through the atrioventricular node, a prolongation of the QT-interval, and a prolongation of the atrial and ventricular myocardial refractoriness always developed. During short-term treatment, these effects were not found, except for depression of the AV-nodal conduction. This led to the suggestion that the electrophysiological effects of amiodarone during long-term treatment might be partly the result of the accumulation of its metabolite desethylamiodarone. Therefore, we examined the electrophysiological effects of amiodarone and desethylamiodarone on conduction and refractoriness in isolated spontaneously beating guinea pig hearts perfused by the method of Langendorff. Within 1 h of perfusion, desethylamiodarone caused a more pronounced prolongation of the AV-nodal, His-bundle, and intraventricular conduction intervals than did amiodarone. Desethylamiodarone, but not amiodarone led to a prolongation of the QT-interval. The refractoriness of sinoatrial-, AV-nodal conduction, and of the atrial myocardium were significantly more prolonged by amiodarone than by desethylamiodarone. Both compounds showed a comparable strong rate-dependent effect on AV-nodal refractoriness. The ventricular refractoriness was similarily prolonged by either compound. These results show that for the class-III effects (i.e., prolongation of repolarization period) observed under chronic treatment of amiodarone the metabolite desethylamiodarone may be responsible. Desethylamiodarone also exerts more pronounced effects on the fast-channel-dependent parts of the conduction system than does amiodarone, a fact indicated by a higher prolongation of His-bundle and intraventricular conduction.

Amiodarone↗
PubMedDate not supplied

Simultaneous in vivo quantitation of vascular endothelial growth factor mRNA splice variants.

Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. In vivo expression of four different VEGF isoforms, consisting of 121, 165, 189 or 206 amino acids, has been found in the human organism, with all isoforms arising from a single gene by alternative mRNA splicing. We developed an assay for simultaneous quantitation of VEGF isoform expression using competitive polymerase chain reaction (PCR). RNA was isolated from cells, reverse transcribed to cDNA and coamplified with a synthetical competitor DNA using VEGF specific primers. Amplification products were analyzed electrophoretically and concentration of VEGF transcripts calculated. Concentration of housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts was quantitated as above, VEGF gene activity is presented as ratio VEGF mRNA to GAPDH mRNA. Using this assay, we were able to detect and quantitate in vivo expression of VEGF121, VEGF165 and VEGF189 by human peripheral blood mononuclear cells (PBMC). These are the first quantitative data of in vivo VEGF expression by PBMC, suggesting a role for them in the maintenance of the vasculature.

Adult↗
PubMedDate not supplied

A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Strong interindividual variations of VEGF plasma levels have been reported previously. Aim of the present study was to search for mutations in the 3' untranslated region (3'-UTR) of the VEGF gene and to analyze their relation to VEGF plasma levels. METHODS: The complete 3'-UTR (nucleotide 700-2622) of the VEGF gene was screened for sequence variations by single-strand conformation polymorphism (SSCP) analysis. Frequencies of mutated alleles were determined in 119 healthy subjects; VEGF plasma levels were analyzed in a subgroup of 23 healthy men aged 18-36 years. RESULTS: Three novel mutations (702 C/T, 936 C/T, 1612 G/A) were found, allele frequencies of 702T, 936T and 1612A were of 0.017, 0.160 and 0.471, respectively. VEGF plasma levels were significantly lower in carriers of the 936T allele (9.1 +/- 2.7 pg/ml, mean +/- SEM) than in noncarriers (28.0 +/- 5.5 pg/ml, p = 0.033), whereas the 702 C/T and the 1612 G/A mutations showed no association with VEGF plasma levels. The 936 C/T exchange led to the loss of a potential binding site for transcription factor AP-4, although the functionality of this binding site remains unclear. CONCLUSION: We have found three common mutations in the VEGF gene; one of them, a 936 C/T exchange, may be an important determinant of VEGF plasma levels.

3' Untranslated Regions↗
PubMedDate not supplied

Risk factors for peripheral atherosclerosis. Retrospective evaluation by stepwise discriminant analysis.

To evaluate the optimal discriminators for peripheral atherosclerosis, we studied retrospectively 49 male patients and 39 male controls between 40 and 60 years of age. In addition to hypertension, cigarette smoking, diabetes mellitus, and hyperuricemia, we determined the most common lipids, lipoproteins, and apolipoproteins. Highly significant differences of median values between patients and controls in decreasing order of magnitude were recorded for apo A-II/apo B, apo A-I/apo B, apo B, total cholesterol, and LDL-cholesterol. A retrospective classification of patients and controls under optimal conditions with one variable (apo A-I/apo B) yielded an error rate of 25%. We found that apolipoproteins were better discriminators for peripheral atherosclerosis than than were lipids or lipoprotein lipids. The application of a linear regression discriminant analysis including 29 variables greatly decreased the rate of error and increased the sensitivity and specificity of the classification. From 229 possible models, we used an economic selection strategy to sort out those which either gave the best segregation or were considered the most practicable. The optimal model with 14 variables gave an error rate of less than 5% for the group studied. Suboptimal models yielded error rates between 13% and 18%. We conclude that a mathematical treatment of laboratory data which includes lipid parameters in addition to apolipoprotein values can improve the classification of peripheral vascular atherosclerosis.

Adult↗