Patricia A. Penkoske

Spatiotemporal evolution of ventricular fibrillation.

Sudden cardiac death is the leading cause of death in the industrialized world, with the majority of such tragedies being due to ventricular fibrillation. Ventricular fibrillation is a frenzied and irregular disturbance of the heart rhythm that quickly renders the heart incapable of sustaining life. Rotors, electrophysiological structures that emit rotating spiral waves, occur in several systems that all share with the heart the functional properties of excitability and refractoriness. These re-entrant waves, seen in numerical solutions of simplified models of cardiac tissue, may occur during ventricular tachycardias,. It has been difficult to detect such forms of re-entry in fibrillating mammalian ventricles. Here we show that, in isolated perfused dog hearts, high spatial and temporal resolution mapping of optical transmembrane potentials can easily detect transiently erupting rotors during the early phase of ventricular fibrillation. This activity is characterized by a relatively high spatiotemporal cross-correlation. During this early fibrillatory interval, frequent wavefront collisions and wavebreak generation are also dominant features. Interestingly, this spatiotemporal pattern undergoes an evolution to a less highly spatially correlated mechanism that lacks the epicardial manifestations of rotors despite continued myocardial perfusion.

Mechanism of cardiac defibrillation in open-chest dogs with unipolar DC-coupled simultaneous activation and shock potential recordings.

The automatic implantable cardioverter-defibrillator has been shown to dramatically improve survival. The future refinement of these devices requires a clear understanding of their mechanism of action. We performed the following study to test two hypotheses: 1) When defibrillation is successful, fibrillating activity must be annihilated in a critical mass of both ventricles; and 2) when defibrillation is unsuccessful, at least one area of the ventricular mass has been left fibrillating. Unipolar Ag/AgCl sintered electrodes were directly coupled from triangular arrays at 40 epicardial locations (total, 120 recording sites) that covered both right and left ventricular surfaces and were designed to measure the voltage gradient generated by the shock at each triangular array as well as the underlying myocardial electrical activity before and immediately after the shock. An algorithm was developed and tested that reliably scored whether a postshock activation was a continuation of the immediately previous fibrillating activity. This technique was applied to 203 defibrillation attempts in six open-chest dogs during electrically induced ventricular fibrillation. There were 139 successful defibrillation attempts and 64 unsuccessful attempts. Monophasic truncated exponential 10-msec defibrillation shocks (0.5-35 J) were delivered through an anodal patch on the right atrium and a cathodal patch on the left ventricular apex. In all cases of unsuccessful defibrillation, at least one ventricular site could be clearly identified that failed to be defibrillated. In cases of successful defibrillation two distinct patterns were observed: 1) complete annihilation of fibrillating activity at all sites or 2) nearly complete cessation of fibrillating activity with a single area of persistent fibrillation that subsequently self-extinguished within one to three activations. This single site in the second form of successful defibrillation was located in the region of minimum voltage gradient produced by the defibrillating waveform and was occasionally accompanied by dynamic encapsulation with refractory tissue as a result of a wavefront emanating from a region that had undergone successful defibrillation. These results support the hypothesis that a critical mass of myocardium must be affected for successful defibrillation and that unsuccessful defibrillation is always accompanied by residual fibrillating activity in at least one site. The results also demonstrate that the size of the critical mass required for successful defibrillation can be less than 100%.

Significance of inwardly directed transmembrane current in determination of local myocardial electrical activation during ventricular fibrillation

Ventricular fibrillation (VF) is the principle cardiac rhythm disorder responsible for sudden cardiac death in humans. The accurate determination of local cardiac activation during VF is essential for its mechanistic elucidation. This has been hampered by the rapidly changing and markedly heterogeneous electrophysiological nature of VF. These difficulties are manifested when attempting to differentiate true propagating electrical activity from electrotonic signals and when identifying local activation from complex and possibly fractionated electrograms. The purpose of this investigation was to test the hypothesis that the presence of a balanced inwardly and outwardly directed transmembrane charge, obtained from the ratio of the inward to outward area under the cardiac transmembrane current curve (-/+ Im area), could reliably differentiate propagating from electrotonic deflections during VF. To test this hypothesis, we applied a recently described technique for the in vivo estimation of the transmembrane current (Im) during cardiac activation. A 17-element orthogonal epicardial electrode array was combined with an immediately adjacent optical fiber array to record electrical and optically coupled transmembrane potential signals during VF. Recordings were obtained during electrically induced VF in six dogs to determine the Im associated with activation and the time course of repolarization, as well as unipolar electrograms and bipolar electrograms recorded at multiple center-to-center interelectrode distances from 0.2 to 3 mm. Propagating local activations were associated with the presence of an easily identified inwardly directed Im, with a balanced inward and outward charge (-/+ Im area approximately 1.0). Electrotonic wave-forms lacked this inward Im (-/+ Im area approximately 0.0). Normal Na(+)-mediated inward currents were directly demonstrated to be responsible for some activations during VF.

Transposition of the Great Arteries and Ventricular Septal Defect: Results with the Senning Operation and Closure of the Ventricular Septal Defect in Infants

From May, 1978, to July, 1982, 46 infants ranging in age from 12 days to 12 months and in weight from 2.1 to 8.4 kg underwent repair of dextrotransposition of the great arteries (D-TGA) and ventricular septal defect (VSD) using a Senning repair and closure of the VSD. Ventricular septal defects were classified as membranous (47.8%), malaligned (28.3%), atrioventricular (AV) canal type (13.0%), subarterial (2.2%), muscular (2.2%), and multiple (6.5%). Hospital mortality was 15.2% and late mortality, 5.1%. Postoperative complications included tricuspid regurgitation (mild in 3 and severe, requiring tricuspid valve replacement, in 3), residual VSD (pulmonary/systemic flow ratio of greater than 2:1) in 3 patients (2, AV canal type and 1, multiple VSDs), pulmonary venous obstruction in 3 patients, and permanent complete heart block in 4 patients (2, AV canal type of VSD also requiring tricuspid valve replacement). Lung biopsy studies showed reversible Heath-Edwards and morphometric changes. No patient was seen with Heath-Edwards III or greater changes. In 10 patients, right ventricular end-diastolic pressures and pulmonary artery pressures at rest were within normal limits one year after operation. As the operative mortality of atrial inversion and arterial switch operations for D-TGA with VSD tends to become comparable, more extensive follow-up data, including cardiac catheterization and coronary arteriography in a large number of patients, will be necessary to establish the superiority of one approach over the other.

Aprotinin in children undergoing repair of congenital heart defects

BACKGROUND Aprotinin use in adults is increasing, and its use in children has recently been reported. METHODS The efficacy of aprotinin in children was tested in 80 children. Patients were in four groups: reoperations (59), neonates (8), extremely cyanotic children (6), and other complex repairs (7). The results were compared with those of 55 control infants and children: reoperations (25), neonates (10), cyanotic (10) and complex (10). Treatment groups were identical in age, sex ratio, cross-clamp time, and bypass time. RESULTS Patients treated with aprotinin had a significant reduction in chest tube drainage (16.5 +/- 9.8 versus 33.4 +/- 22.1 mL.kg-1.h-1; p < 0.001) and time to skin closure (64.2 +/- 23.7 versus 80.1 +/- 24.6 minutes; p < 0.001). Transfusion requirements were decreased in aprotinin-treated patients 4.2 +/- 3.4 versus 6.7 +/- 5.2 donors; p < 0.001). All of the control patients were exposed to at least one donor, whereas 10/80 (12.5%) of the aprotinin-treated group had no blood use (p < 0.006). There were no cases of renal insufficiency or allergic reactions in children receiving aprotinin. Three patients had thrombotic episodes: 2 superior vena caval problems and a lower extremity deep venous thrombosis. There were 3 cases of mediastinitis in the aprotinin group versus none in control patients (p < 0.05). CONCLUSIONS We conclude aprotinin is an effective means of reducing bleeding, operating time, and donor exposure in infants and children. An increased rate of thrombosis and possibly mediastinitis are potential problems.

A method for visualization of ventricular fibrillation: Design of a cooled fiberoptically coupled image intensified CCD data acquisition system incorporating wavelet shrinkage based adaptive filtering.

The measurement of cardiac transmembrane potential changes with voltage sensitive dyes is in increasing use. Detection of these very small fluorescent alterations using large multiplexed arrays, such as charge coupled device (CCD) cameras at high sampling rates, has proven challenging and usually requires significant averaging to improve the signal-to-noise ratio. To minimize the damage of living tissue stained with voltage sensitive dyes, excitation photon exposure must be limited, with the inevitable consequence of diminishing the fluorescence that is generated. State-of-the-art high frame rate CCD cameras have read noise levels in the 5-10 e(-) rms range, which is at least two orders of magnitude above that required to detect voltage sensitive dye alterations at individual pixels corresponding to 1 mm(2) heart regions illuminated with levels of 100 mW/cm(2) at frame rates approaching 1000 frames/sec. Image intensification is thus required prior to photon quantification. We report here the development of such a data acquisition system using commercially available hardware. Additionally, in the past ten years, a mathematical theory of multiresolution has been developed, and new building blocks called wavelets, allow a signal to be observed at different resolutions. Wavelet analysis also makes possible a new method of extricating signals from noise. We have incorporated spatially adaptive filters based on wavelet denoising of individual pixels to significantly reduce the multiple noise sources present in the acquired data. (c) 1998 American Institute of Physics.

Spontaneous Aortic Thrombosis in a Neonate Presenting as Coarctation

Spontaneous aortic thrombosis in the neonate is a rare entity of uncertain etiology with a high mortality. To our knowledge, this is the first report of a newborn surviving surgical treatment of spontaneous thrombosis of the thoracic aorta.

Antimicrobial prophylaxis for open heart operations

Between 1986 and 1988, 450 adults undergoing coronary artery bypass, cardiac valve replacement, or both were enrolled into a prospective, randomized, comparative trial of cephalothin versus cefamandole as perioperative prophylaxis. They were assessed during their hospitalization and at 6 weeks and 6 months after discharge for postoperative infectious complications. Eleven patients had major postoperative infections including 5 with sternal wound infections (three bacteremic), 6 with bacteremia, 1 with prosthetic valve endocarditis, and 3 with severe venous donor graft site infections. Eight major infections occurred in patients receiving cephalothin prophylaxis and three in patients receiving cefamandole, with all five sternal wound infections occurring in the cephalothin group. Postoperative pathogens responsible for the major infections included gram-negative aerobes in 5 patients, Staphylococcus aureus in 4, and Staphylococcus epidermidis in 2. Preoperative colonizing staphylococcal isolates were not predictive of postoperative staphylococcal pathogens. Although there was no statistically significant difference in rate of major postoperative infectious complications using either cephalothin or cefamandole prophylaxis, there was a trend in favor of cefamandole. Gram-negative aerobes are becoming increasingly important pathogens in this setting.

Barium decreases defibrillation energy requirements

Summary Certain antiarrhythmic drugs that inhibit myocardial repolarizing currents decrease defibrillation energy, but the effect of blocking particular currents on defibrillation is not well understood. We therefore investigated the effect of barium, a relatively selective blocker of inwardly rectifying potassium current (Ik1) on voltage and energy requirements for defibrillation in an open-chest dog model. Defibrillation energy and voltage requirements were assessed by delivering monophasic shocks through epicardial electrode patches at varying voltages to construct a dose-response curve of energy and voltage versus success in defibrillation. The energy and voltage for 50% success in defibrillation (E50 and V50, respectively) were determined by logistic regression. Monophasic action potential duration at 90% repolarization (MAPDgo) was measured with a contact electrode, and ventricular refractory period (VERP) was measured. After baseline measurements were obtained of A£so, VJ0, MAPD90, and VERP, saline (control) (n = 6) or barium (1.1 mg/kg/min for 5 min followed by 0.25 mg/kg/min) (n = 11) was administered. Defibrillation voltage and energy requirements and electrophysiologic measures were repeated after 30 and 120 min of barium or saline infusion. In control animals, there was no significant change with time in V50 (2.0 ± 12.4 and −0.2 ± 16.0% at 30 and 120 min, respectively), VERP ( + 3 ± 5 and −2 ± 3% at 30 and 120 min, respectively) or MAPD90 (+1 ± 4 and – 2 ± 6, at 30 and 120 min, respectively). In contrast, after barium infusion, there was a significant decrease in V50 both at 30 and 120 min (-21.8 ± 19.2, −36.2 ± 15.8%, p < 0.001), in E50 (decrease of −34.2 ± 38 and −59.9 ± 23% at 30 and 120 min, respectively, p < 0.001), and increases in VERP (+ 20 ± 4 and + 22 ± 4% at 30 and 120 min, p < 0.03) and in MAPD90 (+ 15 ± 6 and + 15 ± 4% at 30 and 120 min, p < 0.03). We conclude that relatively specific inhibition of inwardly rectifying potassium current markedly decreases defibrillation voltage and energy requirements at a dose that produces slight increases in ventricular refractoriness and MAPD.

A completely automated activation-repolarization interval algorithm for directly coupled unipolar electrograms and its three-dimensional correlation with refractory periods.

Sintered Ag-AgCl needle electrodes were used to record unipolar directly coupled (DC) electrograms transmurally from right and left ventricular myocardium. Direct coupling yields unfiltered low-frequency signal content, preserving repolarization waveform morphology. These electrograms were analyzed using completely automated computer algorithms for the timing of local activation and local repolarization that permit beat-to-beat determinations of these parameters. The local activation to repolarization interval was compared with the refractory period obtained with the extrastimulus technique from the same electrode during varied basic cycle lengths and pacing sequences. Pooling of the activation to refractory period versus activation-to-repolarization data from all sites and pacing sequences produced a correlation coefficient of 0.96, with a standard error of the estimate of 5.1 msec. The results demonstrate that DC-coupled unipolar electrograms may prove useful in direct, three-dimensional local repolarization timing and in simultaneous assessment of the temporal and spatial dispersion of changes in repolarization from multiple sites.