Reducing electrical defibrillation thresholds with glibenclamide in an isolated rabbit heart preparation.

Glibenclamide has been shown to prevent ischemia-induced shortening of action-potential duration (APD) and to prolong effective refractory period (ERP). Glibenclamide also has been shown to prolong APD under normal conditions. The aim of this study was to test the hypothesis that glibenclamide would prolong APD and ERP in the nonischemic heart by blocking adenosine triphosphate-sensitive K+ (K(ATP)) channels in myocardium, thus reducing defibrillation energy requirements. Hearts from 15 adult male New Zealand White rabbits, weight 3.1 +/- 0.1 kg, were perfused with a Krebs-Henseleit solution containing either no drugs (five hearts) or glibenclamide (10 hearts) at six concentrations ranging from 30 nM to 10 microM. Two 140-mm2 Pt-Ir mesh patch electrodes were sutured onto the ventricles. A 3.5/2.5-ms biphasic pulse (impedance, 95 +/- 16 omega) with randomly selected voltages of 20, 30, 50, 70, 90, or 110, defibrillated the heart after 10 s of fibrillation. The APD, ERP, fibrillation threshold (FT), and defibrillation threshold (DFT) were determined from monophasic action potentials, computer-controlled pacing, 50-Hz sinusoidal pacing, and multiple defibrillation shocks, respectively. Defibrillation thresholds were determined from a total of 180 fibrillation and defibrillation sequences, conducted in each preparation, and the results were fitted to a sigmoid dose-response curve by logistic regression analysis. Five repeated observations of APD, ERP, FT, and DFT showed no change over a 5-h period, whereas for DFT, there was a significant increase between first and next four determinations. With glibenclamide (100 and 300 nM, and 1 and 10 microM), a dose-dependent difference (p < 0.05) compared with controls was observed. There was an increase in APD, ERP, and FT and a decrease in DFT at 50% success (V50). The maximal effect for each parameter occurred at 300 nM. Glibenclamide dose-dependently reduced DFT and increased FT in an isolated nonischemic rabbit heart preparation. A probable mechanism is through APD and ERP prolongation by blocking ATP-sensitive K+ channels, suggesting that these channels may be important in modifying the APD and ERP during electrical defibrillation. This might be of particular interest in reducing electrical-defibrillation thresholds, thereby minimizing heart damage.

Transmembrane potentials during high voltage shocks in ischemic cardiac tissue.

Transmembrane, voltage sensitive fluorescent dye (TMF) recording techniques have shown that high voltage shocks (HVS), typically used in defibrillation, produce either hyper- or depolarization of the transmembrane potential (TMP) when delivered in the refractory period of an action potential (AP) in normal cardiac tissue (NT). Further, HVS produce an extension of the AP, which has been hypothesized as a potential mechanism for electrical defibrillation. We examined whether HVS modify TMP of ischemic tissue (IT) in a similar manner. In seven Langendorff rabbit hearts, recordings of APs were obtained in both NT and IT with TMF using di-4-ANEPPS, and diacetylmonoxime (23 microM) to avoid motion artifacts. Local ischemia was produced by occlusion of the LAD, HVS of either biphasic (5 + 5 ms) or (3 + 2 ms) or monophasic shapes (5 ms) were delivered at varying times (20%-90%) of the paced AP. Intracardiac ECG and TMF recordings of the TMP were each amplified, recorded, and digitized at a frequency of 1 kHz. The paced AP in IT was triangular in shape with no obvious phase 3 plateau, typically seen in NT. There was normally a reduced AP amplitude (expressed as fractional fluorescence) in IT (2.6% +/- 1.79%) compared to 3.8% +/- 0.66% in NT, and shortened AP duration (137 +/- 42 vs 171 +/- 11 ms). One hundred-Volt HVS delivered during the refractory period of paced AP in IT in five rabbits, elicited a depolarization response of the TMP with an amplitude up to three times greater than the paced AP. This is in contrast to NT where the 100-V HVS produced hyperpolarization in four hearts, and only a slight depolarization response in one heart. These results suggest that HVS, typically delivered by a defibrillation shock, modify TMPs in a significantly different manner for ischemic cells, which may influence success in defibrillation.

Characterization of shock-induced action potential extension during acute regional ischemia in rabbit hearts.

INTRODUCTION: Defibrillation shocks produce extension of the myocardial action potential repolarization time (AP extension) in nonischemic myocardium. AP extension may synchronize repolarization in the heart because the extension increases when shock timing is increased. We tested whether AP extension occurs and whether it increases when shock timing is increased in regionally ischemic isolated perfused rabbit hearts stained with the transmembrane voltage sensitive fluorescent dye, di-4-ANEPPS and given diacetyl monoxime to eliminate motion artifacts. METHODS AND RESULTS: Before and after left anterior descending (LAD) coronary artery occlusion, APs were recorded on the anterior left ventricular epicardium with an epifluorescence measurement system. Hearts were paced with a train of 10 stimuli (S1) and then during the 10th AP were given a defibrillation shock (S2) from epicardial electrodes on either side of the recording region. Before LAD occlusion, duration of the 9th S1-induced AP measured at full repolarization was 171 +/- 11 msec (mean +/- SD). Within 15 minutes after LAD occlusion, the AP duration became shorter (P < 0.05) and more variable (137 +/- 47 msec), and APs with negligible plateaus were observed. Extension of the 10th AP by S2 was significant both before (mean extension of 59 to 65 msec for three S2 waveforms tested) and after LAD occlusion (mean extension of 35 to 41 msec). Unlike the results before LAD occlusion, AP extension after occlusion was independent of absolute shock timing expressed in msec. When timing was expressed as a fraction of individual AP durations, AP extension after occlusion increased with increases in shock timing. CONCLUSIONS: Shocks extend APs during ischemia; however, absolute time dependence of AP extension is not constant among cells that have different AP durations during ischemia. This may influence postshock repolarization synchrony when different AP durations exist in different parts of regionally ischemic hearts.

Comparison of biphasic and monophasic defibrillation waveforms in an isolated rabbit heart preparation.

STUDY OBJECTIVE: The aims were to develop a Langendorff rabbit heart model and to compare monophasic and biphasic defibrillation pulses. DESIGN: Hearts were perfused with a Krebs-Henseleit solution and two 1.4 cm2 Pt-Ir mesh patch electrodes were sutured onto the ventricles. A 5 ms monophasic or 10 ms biphasic pulse, with randomly selected voltages of 30, 50, 70, 90, 110, or 130 V, defibrillated the heart after 10 s of fibrillation. SUBJECTS: 11 adult male New Zealand white rabbits weighing 2.8(0.27) kg, were used for the studies. MEASUREMENTS AND MAIN RESULTS: A total of 72 fibrillation and defibrillation sequences were conducted in each preparation. The results were fitted to a sigmoidal dose-response curve by logistic regression analysis. Voltage and energy values from the fitted data at 50% and 80% success (V50, V80, E50, E80) indicated a significantly lower (p less than 0.05) defibrillation threshold voltage and energy for the biphasic waveform [V50 = 48 (SD19) V, V80 = 87(27) V, E50 = 0.15(0.12) J, E80 = 0.48(0.29) J] compared with the monophasic waveform [V50 = 79(20) V, V80 = 110(20) V, E50 = 0.27(0.12) J, E80 = 0.5(0.12) J]. There was no observed difference in defibrillation success rate between the first and second halves of any study. CONCLUSIONS: The Langendorff rabbit heart model is suitable for assessing electrical fibrillation and defibrillation mechanisms. Defibrillation can be achieved with a lower energy when using a biphasic rather than a monophasic pulse.

Differences between patients with ventricular tachycardia and ventricular fibrillation as assessed by signal-averaged electrocardiogram, radionuclide ventriculography and cardiac mapping.

This study examined 65 patients with ventricular tachycardia or fibrillation late after myocardial infarction to determine whether they differed with respect to duration of ventricular activation in sinus rhythm and left ventricular ejection fraction. Patients with spontaneous ventricular tachycardia had a longer ventricular activation time in sinus rhythm than did patients with spontaneous ventricular fibrillation. This difference was detected with the signal-averaged electrocardiogram (ECG) (tachycardia 181 +/- 33 ms, fibrillation 152 +/- 23 ms, p less than 0.001) and at epicardial mapping (tachycardia 210 +/- 17 ms, fibrillation 192 +/- 17 ms, p less than 0.02). Left ventricular ejection fraction was lower in patients with spontaneous ventricular tachycardia (0.22 +/- 0.09) than in patients with spontaneous ventricular fibrillation (0.27 +/- 0.09) (p less than 0.05). The patients with both spontaneous and inducible ventricular fibrillation had a shorter ventricular activation time on the signal-averaged ECG (129 +/- 17 ms) and a higher ejection fraction (0.36 +/- 0.05) than did either patients with spontaneous ventricular fibrillation and inducible ventricular tachycardia (158 +/- 21 ms and 0.25 +/- 0.08, respectively, each p less than 0.01) or patients with both spontaneous and inducible ventricular tachycardia (181 +/- 33 ms and 0.22 +/- 0.09, respectively, each p less than 0.001). Of the patients with inducible ventricular tachycardia, presentation with tachycardia rather than fibrillation was associated with a longer ventricular activation time on the signal-averaged ECG (181 +/- 33 versus 158 +/- 21 ms, p less than 0.02) and a longer cycle length of inducible ventricular tachycardia (290 +/- 61 versus 259 +/- 44 ms, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and efficacy of pacing for ventricular tachycardia.

This study was undertaken to determine the safety and efficacy of three different pacing modalities on the termination of ventricular tachyarrhythmias. Thirty-two patients were studied in the electrophysiology laboratory. Three randomized pacing modalities were selected for attempted conversion: auto increment, auto burst, and random burst. In all three groups, arrhythmias with cycle lengths shorter than 230 ms required DC shock, with one exception. Those longer than 230 ms were terminated by pacing in 85% of cases. There was a 15% rate of acceleration. Thus, antitachycardia pacing for ventricular tachyarrhythmias should be considered only with defibrillating back-up.

Histological evaluation of porous titanium cardiac pacemaker electrode tips.

An investigation of the tissue reaction to five porous titanium alloy pacemaker electrode tips inserted in sheep hearts was made. Attachment of the electrode tips to the endocardial wall was facilitated by fibrous tissue ingrowth into the porous material. Vascularized fibrocollagenous tissue was found within the pores of the tips. One tip was found to be infected. The presence of occasional multinucleated foreign-body giant cells within the porosity was related to the particulate features of the porous tip. The electrode tips had a reduced sensing impedance compared with conventional solid platinum tips. The present findings are consistent with previous observations relating to porous cobalt-chromium alloy and porous platinum-iridium alloy tips and suggest that porous titanium alloy may be a suitable pacemaker electrode tip material.

Characteristics of advanced porous and textured surface pacemaker electrodes.

Reduced stimulation thresholds, improved sensing and better attachment have been claimed for totally porous and porous surfaced electrodes. In this study, the potential for clinical use of two new types of porous electrodes and a non-porous, textured high microsurface area electrode, has been evaluated by comparison with equivalent sized, smooth non-porous controls. Eighteen sintered and seven laser drilled porous electrodes, seven-non-porous textured electrodes, and sixteen controls, were implanted singly in the right ventricles of sheep. Measurements of threshold, pacing, sensing and bulk impedances were taken at regular intervals for up 180 days. At sacrifice, only three of the thirteen non-porous controls were attached. All laser porous electrodes, apart from two which were dislodged, were attached, as were eleven of fifteen sintered porous, and five of seven textured non-porous electrodes. Tissue ingrowth was found for both porous electrode types. Stimulation thresholds were not statistically different for all electrode types (p less than 0.05). Pacing and bulk impedances of the two porous and surface textured electrodes were significantly higher (p less than 0.10, p less than 0.05, respectively) than those of controls. The three new electrodes exhibited similar chronic sensing impedance values, 30% less than equivalent non-porous electrodes. The similar sensing performance of the porous and high microsurface area non-porous electrodes indicates that the nature of the external surface, rather than internal porosity, determines sensing impedance. All three new electrode types showed improved attachment and sensing compared with similar smooth electrodes. The laser porous electrode, which permits fixation by tissue ingrowth and maintains simplicity of construction, is promising for routine clinical use.

Screening of solid and porous materials for pacemaker electrodes.

Several different materials, including one which was porous, were studied to assess their properties as pacemaker electrode tips. Leads were implanted in sheep for periods up to one year. Electrical measurements were made during the implant period and histopathological examination performed after sacrifice. Although titanium vapor-deposited carbon, and silver did not lower the chronic stimulation threshold below that of platinum, their electrical characteristics were within generally acceptable limits. Zinc evoked a severe tissue reactions and a high threshold. Porous titanium alloy electrodes demonstrated reduced dislodgement, more frequent attachment and a lower sensing impedance than other electrodes.

A new pressure measuring system for cushins and beds--with a review of the literature.

An interface pressure measuring device for the assessment of subject-cushion interface pressures at ten points has been described. Preliminary trials using 12 healthy subjects on four cushions and three spinal injury patients on six cushings, has been carried out. It was also found that the water and foam cushion distributed the pressure over a large area than the foam cushions.