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Biomedical subjects

R A Gray

Publications and source records attributed to R A Gray.

At least 19 recordsLinked to original sources
PubMed2005

Long-term survival of surgically treated hip fracture in an Australian regional hospital.

This study was undertaken to identify factors influencing outcome in elderly patients operated for hip fracture. In particular, this study examined factors related to mortality at least 30 months post-fracture. Hospital records and death registrations were analysed for 463 patients aged 60 or more years treated for hip fracture at a Queensland regional hospital between 1997 and 2001. The overall mortality for surgically treated patients was 13.7% at 100 days and 24.9% at one year Patient factors including age, gender, health status and place of residence were the predominant influences on mortality. Non-patient and process factors including delay to surgery, type of operation and type of anaesthetic had minimal impact on mortality. No major determinants of length of hospital stay were identified. Patient health status was the main determinant for surgical delay. Our results confirm the persistently high mortality in this group of patients, and suggest that the main determinants of outcome are patient- rather than process-related.

Age Distribution↗
PubMed2003

Transurethral vaporisation of the prostate and irrigating fluid absorption.

Transurethral vaporisation of the prostate gland (TUVP) is an emerging surgical alternative to conventional electroresection (TURP). This study examined vesical pressure and fluid absorption during TUVP in 35 patients with benign prostatic hypertrophy. The irrigating fluid was a solution of glycine 1.5% and ethanol 1%. Intraoperative intravesical pressure was monitored continuously and absorption of irrigating fluid was detected by ethanol analysis in expired breath. The incidence of absorption during TUVP was 34%. Intravesical pressures were higher amongst patients who went on to absorb than amongst patients who did not. Combining data from the current study and from 35 patients in our previous investigation into TURP (Gray et al.: Anaesthesia 2001; 56: 461-4), urological trainees operated at higher mean pressure and for longer than their consultant colleagues and their resections were significantly more likely to result in absorption. The incidence of irrigating fluid absorption during trainees' operations appeared to be less using TUVP than using conventional TURP.

Absorption↗
PubMed2001

Standing excitation waves in the heart induced by strong alternating electric fields.

We studied the effect of sinusoidal electric fields on cardiac tissue both experimentally and numerically. We found that periodic forcing at 5-20 Hz using voltage applied in the bathing solution could stop the propagation of excitation waves by producing standing waves of membrane depolarization. These patterns were independent of the driving frequency in contrast to classical standing waves. The stimulus strength required for pattern formation was large compared to the excitation threshold. A novel tridomain representation of cardiac tissue was required to reproduce this behavior numerically.

Algorithms↗
PubMed2001

Mechanism of ventricular defibrillation for near-defibrillation threshold shocks: a whole-heart optical mapping study in swine.

BACKGROUND: To study the mechanism by which shocks succeed (SDF) or fail (FDF) to defibrillate, global cardiac activation and recovery and their relationship to defibrillation outcome were investigated for shock strengths with approximately equal SDF and FDF outcomes (DFT(50)). METHODS AND RESULTS: In 6 isolated pig hearts, dual-camera video imaging was used to record optically from approximately 8000 sites on the anterior and posterior ventricular surfaces before and after 10 DFT(50) biphasic shocks. The interval between the shock and the last ventricular fibrillation activation preceding the shock (coupling interval, CI) and the time from shock onset to 90% repolarization of the immediate postshock action potential (RT(90)) were determined at all sites. Of 60 shocks, 31 were SDF. The CI (59+/-7 versus 52+/-6 ms) and RT(90) (108+/-19 versus 88+/-8 ms) were significantly longer for SDF than FDF episodes. Spatial dispersions of CI (36+/-5 versus 34+/-3 ms) and RT(90) (40+/-16 versus 40+/-8 ms) were not significantly different for SDF versus FDF episodes. The first global activation cycle appeared focally on the left ventricular apical epicardium 78+/-32 ms after the shock. CONCLUSIONS: For near-threshold shocks, defibrillation outcome correlates with the electrical state of the heart at the time of the shock and on RT. Global dispersion of RT was similar in both SDF and FDF episodes, suggesting that it is not crucial in determining defibrillation outcome after DFT(50) shocks.

Animals↗
PubMed2001

Intravesical pressure and the TUR syndrome.

Intravesical pressure was measured continuously during 35 transurethral prostate resections using a fine suprapubic catheter. Absorption of irrigating fluid was detected by tagging it with ethanol and sampling the expired breath using an alcohol meter. Higher mean (SD) intravesical pressure was demonstrated in those patients who absorbed irrigating fluid (19.1 (7.7) mmHg) than in those who did not (12.4 (6.5) mmHg; p = 0.00004). Higher peak pressures were also demonstrated among absorbing patients. Traditional risk factors for fluid absorption, such as operator experience and resectate mass, were found to correlate with pressure exposure over time. Exposure to supranormal bladder pressure over time is the final common path for all causes of absorption. Vesical pressure monitoring may be a valuable feedback tool during difficult resections or operator training.

Absorption↗
PubMed2001

Effect of strength and timing of transmembrane current pulses on isolated ventricular myocytes.

INTRODUCTION: Little is known about how the amplitude and timing of transmembrane current pulses affect transmembrane potential (Vm) and action potential duration (APD) in isolated myocytes. METHODS AND RESULTS: Ten ventricular myocytes were isolated from five rabbit hearts. Each cell was paced at an S1 cycle length of 250 msec, and S2 pulses of 10-msec duration were delivered at various strengths and time intervals. For all S2 strengths (0.2 to 1.5 nA), the magnitude of changes in Vm did not depend on polarity during the plateau, but were larger for depolarizing pulses during phase 3 repolarization. However, the magnitude of changes in APD varied with polarity during the entire action potential for strengths ranging from 0.5 to 1.5 nA. Greater changes in APD occurred for hyperpolarizing pulses during the plateau and depolarizing pulses during phase 3. In addition, we used a cardiac phase variable to quantify the current threshold for regenerative depolarization and repolarization as a function of prestimulus Vm. Regenerative depolarization occurred during phase 3 repolarization, and its current threshold was less than that required for regenerative repolarization that occurred during the plateau. These data were compared to computer simulations in a patch of membrane represented by Luo-Rudy dynamic kinetics, and the results were qualitatively similar, including the higher threshold for regenerative repolarization compared to regenerative depolarization. CONCLUSION: This characterization of the nonlinear response of isolated cells to transmembrane current, including phase resetting, should aid in understanding the mechanisms of defibrillation because shock-induced changes in Vm and APD have been implicated as important factors in determining defibrillation success.

Action Potentials↗
PubMed2001

Entrainment by an extracellular AC stimulus in a computational model of cardiac tissue.

INTRODUCTION: Cardiac tissue can be entrained when subjected to sinusoidal stimuli, often responding with action potentials sustained for the duration of the stimulus. To investigate mechanisms responsible for both entrainment and extended action potential duration, computer simulations of a two-dimensional grid of cardiac cells subjected to sinusoidal extracellular stimulation were performed. METHODS AND RESULTS: The tissue is represented as a bidomain with unequal anisotropy ratios. Cardiac membrane dynamics are governed by a modified Beeler-Reuter model. The stimulus, delivered by a bipolar electrode, has a duration of 750 to 1,000 msec, an amplitude range of 800 to 3,200 microA/cm, and a frequency range of 10 to 60 Hz. The applied stimuli create virtual electrode polarization (VEP) throughout the sheet. The simulations demonstrate that periodic extracellular stimulation results in entrainment of the tissue. This phase-locking of the membrane potential to the stimulus is dependent on the location in the sheet and the magnitude of the stimulus. Near the electrodes, the oscillations are 1:1 or 1:2 phase-locked; at the middle of the sheet, the oscillations are 1:2 or 1:4 phase-locked and occur on the extended plateau of an action potential. The 1:2 behavior near the electrodes is due to periodic change in the voltage gradient between VEP of opposite polarity; at the middle of the sheet, it is due to spread of electrotonic current following the collision of a propagating wave with refractory tissue. CONCLUSION: The simulations suggest that formation of VEP in cardiac tissue subjected to periodic extracellular stimulation is of paramount importance to tissue entrainment and formation of an extended oscillatory action potential plateau.

Action Potentials↗
PubMed2001

An experimentalist's approach to accurate localization of phase singularities during reentry.

A phase variable that uniquely represents the time course of the action potential has been used to study the mechanisms of cardiac fibrillation. A spatial phase singularity (PS) occurs during reentrant wave propagation and represents the organizing center of the rotating wave. Here, we present an error analysis to investigate how well PSs can be localized. Computer simulations of rotating spiral waves scaled appropriately for cardiac tissue were studied with various levels of noise added. The accuracy in identifying and localizing singularities depended on three factors: (i) the point chosen as the origin in state space used to calculate the phase variable; (ii) signal to noise ratio; and (iii) discretization (number of levels used to represent data). We found that for both simulation as well as experimental data, there existed a wide range for the choice of origin for which PSs could be identified. Discretization coupled with noise affected this range adversely. However, there always existed a range for choice of the origin that was 20% or more of the action potential amplitude within which the accuracy of localizing PSs was better than 2 mm. Thus, a precise determination of origin was not necessary for accurately identifying PSs.

Algorithms↗
PubMed2000

A mechanism of transition from ventricular fibrillation to tachycardia : effect of calcium channel blockade on the dynamics of rotating waves.

Abbreviation of the action potential duration and/or effective refractory period (ERP) is thought to decrease the cycle length of reentrant arrhythmias. Verapamil, however, paradoxically converts ventricular fibrillation (VF) to ventricular tachycardia (VT), despite reducing the ERP. This mechanism remains unclear. We hypothesize that the size and the dynamics of the core of rotating waves, in addition to the ERP, influence the arrhythmia manifestation (ie, VF or VT). The objectives of this study were (1) to demonstrate functional reentry as a mechanism of VF and VT in the isolated Langendorff-perfused rabbit heart in the absence of an electromechanical uncoupler and (2) to elucidate the mechanism of verapamil-induced conversion of VF to VT. We used high-resolution video imaging with a fluorescent dye, ECG, frequency and 2-dimensional phase analysis, and computer simulations. Activation patterns in 10 hearts were studied during control, verapamil perfusion (2x10(-6) mol/L), and washout. The dominant frequency of VF decreased from 16.2+/-0.7 to 13.5+/-0.6 Hz at 20 minutes of verapamil perfusion (P<0.007). Concomitantly, phase analysis revealed that wavefront fragmentation was reduced, as demonstrated by a 3-fold reduction in the density of phase singularities (PSs) on the ventricular epicardial surface (PS density: control, 1.04+/-0.12 PSs/cm(2); verapamil, 0.32+/-0.06 PSs/cm(2) [P=0.0008]). On washout, the dominant frequency and the PS density increased, and the arrhythmia reverted to VF. The core area of transiently appearing rotors significantly increased during verapamil perfusion (control, 4.5+/-0.6 mm(2); verapamil, 9.2+/-0.5 mm(2) [P=0.0002]). In computer simulations, blockade of slow inward current also caused an increase in the core size. Rotating waves underlie VF and VT in the isolated rabbit heart. Verapamil-induced VF-to-VT conversion is most likely due to a reduction in the frequency of rotors and a decrease in wavefront fragmentation that lessens fibrillatory propagation away from the rotor.

Animals↗
PubMed2000

Dynamics of wavelets and their role in atrial fibrillation in the isolated sheep heart.

BACKGROUND: The multiple wavelet hypothesis is the most commonly accepted mechanism underlying atrial fibrillation (AF). However, high frequency periodic activity has recently been suggested to underlie atrial fibrillation in the isolated sheep heart. We hypothesized that in this model, multiple wavelets during AF are generated by fibrillatory conduction away from periodic sources and by themselves may not be essential for AF maintenance. METHODS AND RESULTS: We have used a new method of phase mapping that enables identification of phase singularities (PSs), which flank individual wavelets during sustained AF. The approach enabled characterization of the initiation, termination, and lifespan of wavelets formed as a result of wavebreaks, which are created by the interaction of wave fronts with functional and anatomical obstacles in their path. AF was induced in six Langendorff-perfused sheep hearts in the presence of acetylcholine. High resolution video imaging was utilized in the presence of a voltage sensitive dye; two-dimensional phase maps were constructed from optical recordings. The major results were as follows: (1) the critical inter-PS/wavelet distance for the formation of rotors was 4 mm, (2) the spatial distribution of wavelets/PSs was non-random. (3) the lifespan of PSs/wavelets was short; 98% of PSs/wavelets existed for < 1 rotation, and (4) the mean number of waves that entered our mapping field (15.7 +/- 1.6) exceeded the mean number of waves that exited it (9.7 +/- 1.5; P < 0.001). CONCLUSIONS: Our results strongly suggest that multiple wavelets may result from breakup of high frequency organized waves in the isolated Langendorff-perfused sheep heart, and as such are not a robust mechanism for the maintenance of AF in our model.

Acetylcholine↗
PubMed2000

Virtual electrodes and deexcitation: new insights into fibrillation induction and defibrillation.

Previous models of fibrillation induction and defibrillation stressed the contribution of depolarization during the response of the heart to a shock. This article reviews recent evidence suggesting that comprehending the role of negative polarization (hyperpolarization) also is crucial for understanding the response to a shock. Negative polarization can "deexcite" cardiac cells, creating regions of excitable tissue through which wavefronts can propagate. These wavefronts can result in new reentrant circuits, inducing fibrillation or causing defibrillation to fail. In addition, deexcitation can lead to rapid propagation through newly excitable regions, resulting in the elimination of excitable gaps soon after the shock and causing defibrillation to succeed.

Computer Simulation↗
PubMed1999

Shock-induced figure-of-eight reentry in the isolated rabbit heart.

The patterns of transmembrane potential on the whole heart during and immediately after fibrillation-inducing shocks are unknown. To study arrhythmia induction, we recorded transmembrane activity from the anterior and posterior epicardial surface of the isolated rabbit heart simultaneously using 2 charge-coupled device cameras (32,512 pixels, 480 frames/second). Isolated hearts were paced from the apex at a cycle length of 250 ms. Two shock coils positioned inside the right ventricle (-) and atop the left atrium (+) delivered shocks at 3 strengths (0.75, 1.5, and 2.25 A) and 6 coupling intervals (130 to 230 ms). The patterns of depolarization and repolarization were similar, as is evident in the uniformity of action potential duration at 75% repolarization (131.4¿8.3 ms). At short coupling intervals (<180 ms), shocks hyperpolarized a large portion of the ventricles and produced a pair of counterrotating waves, one on each side of the heart. The first beat after the shock was reentrant in 90% of short coupling interval episodes. At long coupling intervals (>180 ms), increasingly stronger shocks depolarized an increasingly larger portion of the heart. The first beat after the shock was reentrant in 18% of long coupling interval episodes. Arrhythmias were most often induced at short coupling intervals (98%) than at long coupling intervals (35%). The effect and outcome of the shock were related to the refractory state of the heart at the time of the shock. Hyperpolarization occurred at short coupling intervals, whereas depolarization occurred at long coupling intervals. Consistent with the "critical point" hypothesis, increasing shock strength and coupling interval moved the location where reentry formed (away from the shock electrode and pacing electrode, respectively).

Action Potentials↗
PubMed1999

Electrophysiological characterisation of the dentate gyrus in five inbred strains of mouse.

Transgenic or knockout mouse models provide the opportunity to study the function of disease-related or novel genes. However, a confounding factor in all such research is the genetic and phenotypic variation of the mouse strain used to construct the models. A trait which is frequently studied in transgenic models of neurological disorders is synaptic transmission and plasticity of the dentate gyrus of the hippocampus. Consequently, we have investigated the variation in this trait across five strains of mouse (129 Ola, C3H, C57 albino, DBA/2, and FVB/N), in vivo. 129 Ola mice were found to have significantly larger maximal evoked EPSP slope and population spike amplitudes compared to the other strains. No differences across strains were found in paired-pulse facilitation of EPSP slope, a measure of pre-synaptic short-term plasticity. DBA/2 mice showed significantly reduced paired-pulse inhibition of population spike, a measure of poly-synaptic inhibitory feedback within the dentate gyrus. Potentiation of EPSP and population spike, following tetanic stimulation of the perforant path, was observed in all strains. However, DBA/2 mice showed a deficit in the maintenance of potentiation over 1 h, which confirms a previous report [S. Matsuyama, U. Namgung, A. Routtenberg, Long-term potentiation persistence greater in C57BL/6 than DBA/2 mice: predicted on basis of protein kinase C levels and learning performance, Brain Res. 763 (1997) 127-130]. These results show that electrophysiological traits do vary significantly across mouse strains, and that the selection of the strain may have a significant impact on results. Furthermore, since production of a transgenic or knock-out mouse frequently requires cross-breeding, care should be taken in establishing the contribution of parent strains to the final phenotype, as well as the potential interaction with the phenotype arising from the knock-out or transgene.

Analysis of Variance↗
PubMed1999

Sinusoidal stimulation of myocardial tissue: effects on single cells.

INTRODUCTION: Cardiac tissue subjected to sinusoidal stimulus is characterized by action potentials (APs) that have extended plateau phases, sustained for the duration of the stimulus. Extended action potential durations (APDs) are beneficial because they disrupt wandering wavelets in the fibrillating heart. To investigate the mechanisms by which periodic stimulus affects cardiac tissue, particularly the development of sustained depolarization, computer simulations of single cardiac cells exposed to alternating current (AC) are performed. METHODS AND RESULTS: Two modes of stimulation of the cell are examined: external field stimulation and transmembrane current injection. Several membrane models, including Luo-Rudy I and II, are used in the simulations. External AC field stimuli increase the APD of the single cell. The extended plateau of the cellular AP is characterized by periodic oscillations that are 1:2 phase locked with the applied stimulus. This specific behavior is due to the variations in stimulus magnitude and polarity along the cell border, which elicit opposite electrical responses from the cell sides. These pointwise responses are averaged in the macroscopic cellular response and result in sustained oscillatory depolarization that lasts for the duration of the stimulus. In contrast, the cell undergoing current injection does not develop an extended APD. CONCLUSION: The simulations demonstrate that variation of membrane potential within a cell is of paramount importance to the formation of an extended AP plateau in response to AC stimulation.

Action Potentials↗
PubMed1998

Effects of postshock atrial pacing on atrial defibrillation outcome in the isolated sheep heart.

BACKGROUND: Failed atrial defibrillation shocks are associated with organization of postshock activity and a substantial postshock electrical quiescence. We investigated the ability of a train of pacing stimuli to capture or locally entrain atrial myocardium during the quiescent period after low-energy shocks and to alter defibrillation outcome. METHODS AND RESULTS: High-resolution video imaging of near-defibrillation-threshold atrial shocks was performed in 12 Langendorff-perfused sheep hearts. A train of 10 pacing stimuli (10-ms pulse width, 200-ms cycle length) was coupled to the shock at various delays in 7 hearts. Coupling intervals of 40 to 130 ms were investigated for feasibility of capture of the first pacing stimulus. The success rate of capture was 0, 0.08+/-0.08, 0.43+/-0.13, 0.73+/-0.13, and 0.11+/-0.1 for 40-, 60-, 80-, 100-, and 120-ms coupling intervals, respectively (P<0.001). In 5 experiments, the coupling interval was fixed at 100 ms (highest success, see above), and the pacing stimulus amplitude was varied between 1.0, 2.0, and 4.0 V. Successful capture rates were 0.38+/-0.08, 0.75+/-0.08, and 0.64+/-0.08, respectively (P<0.003 for 1.0 versus 2.0 V, P=0.2 for 2.0 versus 4.0 V). Rates of successful defibrillation for the groups without and with pacing were 0.56+/-0.07 and 0.64+/-0.04, respectively (P=0.3). With capture of the first pacing stimulus, the rate of successful defibrillation rose to 0.75+/-0.05 (P<0.01); it remained unchanged without capture (0.48+/-0.07 versus 0.56+/-0.07 for no pacing). CONCLUSIONS: Pacing during the quiescent period that follows defibrillation shocks is feasible. A pacing train whose first pacing stimulus successfully captures during the quiescent period of near-defibrillation-threshold shocks appears to alter the outcome.

Animals↗