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M Killian

Publications and source records attributed to M Killian.

9 recordsLinked to original sources
PubMed2001

Methods for determining the refractory period and excitable gap during persistent atrial fibrillation in the goat.

BACKGROUND: Recently, the temporal excitable gap during atrial fibrillation (AF) has been identified as a vulnerable parameter for cardioversion of AF. In this study, we evaluated 5 methods to measure the refractory period (RP(AF)) and the excitable period (EP(AF)) during persistent AF. METHODS AND RESULTS: In 11 goats instrumented with 83 epicardial atrial electrodes, persistent AF (43+/-34 days) was induced with a median AF cycle length (CL) of 98+/-14 ms. To measure RP(AF), premature stimuli were applied to the center of the electrode array on the right or left atrium. The RP(AF) measured by mapping of premature stimuli was 70+/-12 ms ("gold standard"). The RP(AF) determined during entrainment of AF was 77+/-17 ms (R(2)=0.88, P<0.01). Statistical analysis of the effects of synchronized stimuli (each coupling interval x100) on the AFCL histogram yielded an RP(AF) of 70+/-13 ms (R(2)=0.94, P<0.01). A further simplification was to apply slow fixed-rate pacing (1 Hz) during AF. For each stimulus (n=250 to 500), the paced AFCL was plotted against its coupling interval, and capture was determined by statistical shortening of the AFCL (RP(AF) 71+/-17 ms, R(2)=0.84, P<0.01). The 5th percentile of the AFCL histogram as an index of RP(AF) was 77+/-12 ms (R(2)=0.90, P<0.01). CONCLUSIONS: During persistent AF with an AFCL of 98+/-14 ms, the RP(AF) determined by mapping of synchronized premature stimuli (gold standard) was 70+/-12 ms, with an excitable period of 28+/-8 ms. Although the indirect methods to measure RP(AF) all correlated well with the gold standard, slow fixed-rate pacing seems to be the most attractive technique because of the ease of acquiring the data and the clear graphic result.

Animals↗
PubMed1999

Repetitive electrical remodeling by paroxysms of atrial fibrillation in the goat: no cumulative effect on inducibility or stability of atrial fibrillation.

INTRODUCTION: Episodes of atrial fibrillation (AF) are known to cause both a rapid reduction in atrial refractoriness (atrial electrical remodeling) and a more delayed increase in AF stability in the chronic goat model. The aims of this study were to examine (1) the hypothesis that an AF-induced increase in AF stability might be due to a mechanism with a longer onset and offset than that of changes in refractoriness and (2) the possibility that repeated paroxysms of maintained AF might cause a cumulative increase in AF stability independent of changes in atrial refractoriness. METHODS AND RESULTS: AF was maintained by rapid atrial pacing in seven goats for three consecutive 5-day periods, each separated from each other by 48 hours of sinus rhythm. Assessments of atrial refractory periods, conduction velocity, AF inducibility, and duration of individual episodes of AF were attempted at intervals throughout the protocol. Forty-eight hours of sinus rhythm was just sufficient for refractoriness changes to fully reverse in all goats, with no evidence of any "residual" increase in AF inducibility. There was no significant difference among any of the three periods of pacing-maintained AF with regard to time to develop episodes of AF of 60-second duration (22.1+/-13, 23.8+/-16, and 30.3+/-29 hours), 1-hour duration (56.6+/-28, 61.3+/-31, and 60.1+/-32 hours), or 24-hour duration (84.0+/-31, 87.0+/-33, and 83.5+/-32 hours). CONCLUSION: There is no evidence for a cumulative effect of AF paroxysms on AF inducibility or stability independent of changes in refractoriness. These findings highlight the importance of atrial refractoriness as a potential target for antiarrhythmic strategies aimed at inhibiting the self-perpetuation of AF.

Action Potentials↗
PubMed1995

Reversal of multiple drug resistance in vitro by phosphorothioate oligonucleotides and ribozymes.

In the present study we investigated the effectiveness of 14, 15 and 18 nucleotide antisense phosphorothioate oligonucleotides (S-ODNs) directed to four different regions of the published mdr-1 gene sequence to reduce the level of mdr-1 gene product (p170, P-glycoprotein) and its function in the over-expressing cell lines Lo-VoDxR, S180DxR and KBChR8-5. The highest efficiency in reduction of multiple drug resistance was obtained at a concentration of 2 microM. In proliferation assays a growth reduction of 50% was observed after exposure of doxorubicin-resistant cells to S-ODN3. p170 protein expression of the resistant cell line LoVoDxR was reduced to the level of the sensitive cell line LoVo as shown by Western blot analysis. S-ODN3 reduced the ID50 of the two human cell lines up to 60% (LoVoDxR) and 21% (KBChR8-5), respectively, but showed no effect in the murine cell line S180DxR. In contrast, S-ODN1 was most effective in the murine system (67% reduction of the ID50), less effective in LoVoDxR (34%) and exhibited no effect in cell line KBChR8-5. Based on the results with the antisense oligonucleotides, a ribozyme directed against the mRNA target region of S-ODN3 was designed. This ribozyme was able to reduce the mdr-1 mRNA in total RNA preparations from cell line LoVoDxR up to 80% after an incubation time of 6 h in the presence of 10 mM MgCl2 at pH 7.5. A modified ribozyme was investigated in cell culture and reduced chemo-resistance of the resistant cell line LoVoDxR and ex vivo cultured blasts of acute myeloid leukemia patients up to 50%.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Reduction of erbB2 gene product in mamma carcinoma cell lines by erbB2 mRNA-specific and tyrosine kinase consensus phosphorothioate antisense oligonucleotides.

A considerable reduction of up to 75% at the protein level of the erbB2 gene product was observed using phosphorothioate antisense oligonucleotides directed against specific sequences of the erbB2 mRNA. Antisense oligonucleotides used were the 14-mer (translation start region) and the 17-mer (3' translated region) all-phosphorothioate oligonucleotides (S-ODNs). Sense or random sequences were used as a control. The greatest reduction at the erbB2 protein level was obtained after a 24h incubation with a single dose of 2 microM antisense S-ODN. The erbB2-mRNA-specific and the tyrosine kinase consensus antisense S-ODNs were comparably effective in inhibiting erbB2 expression. Addition of the transfection reagent DOTAP diminished the efficiency of erbB2 protein reduction by antisense S-ODNs after an incubation period of 24h but was more effective after 48h compared to the application of antisense S-ODNs alone.

Base Sequence↗
PubMed1988

Distinct mechanisms of interferon-gamma and tumor necrosis factor-alpha action in oncogene-transformed mouse fibroblasts.

The potential mechanisms of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha action on tumor cells have been investigated in a model of mouse fibroblasts transformed by distinct retroviral vectors carrying the v-mos, c-myc, and v-Ha-ras oncogene, respectively. Treatment with both cytokines not only caused growth inhibition of v-mos- and c-myc-transformants, but also a reversion of transformation-induced suppression of major histocompatibility complex (MHC) class I antigen expression in all transformed cell lines. The phenotypical reversion of transformants was preceded by a selective modulation of LTR-controlled oncogene expression. TNF-alpha primarily affected stability of oncogene-specific RNAs without influencing the activity of retroviral promoters. In contrast, IFN-gamma was effective at the transcriptional level, apparently due to inhibition of LTR activity as revealed from reduced CAT activity in IFN-gamma-treated LTR-CAT transformants. This IFN-gamma-mediated down-regulation of retroviral promoter activity seemed to be selective for Moloney-virus-derived promoters, since the activity of other viral and cellular promoters was not suppressed by IFN-gamma.

Animals↗
PubMed1988

Angiotensin II reduces voluntary alcohol intake in the rat.

The voluntary intake of alcohol has been shown to be attenuated by a variety of manipulations which increase activity in the renin-angiotensin system. In the present study we examined the effects of peripheral injections of the peptide angiotensin II on alcohol drinking. The peptide produced a dose-dependent decrease in alcohol intake with 20 micrograms/kg having little effect, 200 micrograms/kg reducing intake by approximately 50% and 1 mg/kg virtually abolishing all alcohol drinking. This decrease was not due to a peptide induced motor deficit, or state of sickness, and could also not be accounted for by the increased water intake, or by a change in pharmacokinetics and taste function. These data provide direct evidence that angiotensin II can modulate voluntary alcohol drinking. The possibility that the level of angiotensin II serves as a satiety signal in alcohol drinking is discussed.

Alcohol Drinking↗
PubMed1986

Five-year performance of the Medtronic 6971 polyurethane endocardial electrode.

There is a considerable debate over the long-term performance of polyurethane electrodes. Observation to date has demonstrated surface cracking and some clinical failures in patients. Since 1978 we have implanted about 82 6971 Unipolar Medtronic electrodes in the ventricle. In 33 patients, lead integrity was assessed by chronic thresholds determined by decreasing pulse width and pulse amplitude. Sensing functions were assessed by electrocardiographic rhythm analysis. At a follow-up between 7 and 67 months, chronic thresholds at 2.50 volts were 0.08 +/- 0.04 milliseconds in 26 patients with Medtronic Pulse generators (Models 8423, 5985, and 7000). In two patients with similar units, no loss of capture was seen even at 0.05 milliseconds. Three patients, one with Cordis Unit (233F) showed loss of capture at 0.20 milliseconds at 2.00 MA, the other with a Pacesetter unit (255-6) showed loss of capture at 0.20 milliseconds, at 2.50 volts. One patient with Intermedics unit (283) lost capture at 0.07 milliseconds at 2.70 volts. Insulation breaks seen in two patients were demonstrated by pectoral stimulation and pacemaker oversensing. In addition, 24-hour long-term electrocardiographic monitoring was performed in 22 patients between 23 to 70 months. Appropriate pacemaker function was seen except in one patient who demonstrated oversensing. Interruption in insulation was demonstrated at the ligature site at exploration. Thus, in this series of patients who were paced in the ventricle by the 6971 Medtronic electrode, only two patients have demonstrated insulation failure. The incidence of insulation break in this polyurethane unipolar electrode is uncommon and occurs at further stress points.

Electrodes, Implanted↗
PubMed1976

Halo apparatus.

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Humans↗