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Biomedical subjects

F J van Capelle

Publications and source records attributed to F J van Capelle.

At least 19 recordsLinked to original sources

Deconvolution and wavelet-based methods for membrane current estimation from simulated fractionated electrograms.

In infarcted myocardium, extracellular recordings exhibit multiple deflections due to irregular pathway of the electric impulse. In this work the problem of distinguishing local from distant deflections is tackled. In order to evaluate the proposed methods in a controlled setting, simulated data are used, following both Beeler-Reuter and Luo-Rudy kinetics. The input is an array of electrograms positioned on grid-points of a rectangular grid and the output is an array of estimates of the membrane current. First, deconvolution techniques are used in the form of spatial filtering for membrane current estimation from the extracellular recordings. Second, the extracellular recordings undergo wavelet based transformation, followed by a spatial filter which enhances local activity deflections and suppresses distant activity deflections. It is shown that wavelet filtering of the extracellular recordings acts as an evaluator of the efficiency of the deconvolution techniques for the membrane current estimation. Subsequently, activation times based on the results from the two methods are used for the reconstruction of the propagation pattern in a zig-zag case in two-dimensional grids. It is shown that the wavelet-based method is more robust, and can work well even in cases where the grid interval in the y direction is four times larger than the single cell size.

Algorithms↗

Laplacian electrograms and the interpretation of complex ventricular activation patterns during ventricular fibrillation.

INTRODUCTION: During ventricular fibrillation (VF), interpretation of a local electrogram and determination of the local activation moment are hampered by remote activity or intervening repolarization waves. Successful defibrillation depends on critical timing of the shock relative to local activation. We tested the applicability of Laplacian electrograms for detection of the moment of local activation during VF. METHODS AND RESULTS: From isolated perfused porcine intact hearts, 247 local unipolar electrograms were recorded simultaneously (13 x 19 matrix, interelectrode distance 0.3 mm) from the left ventricular wall during sinus rhythm, following pacing or during VF. Activation maps were constructed based on local unipolar electrograms, and Laplacian electrograms were calculated from local electrograms and its eight neighbors. The Laplacian electrogram displayed a sharp R/S complex with local activation indicated by the moment of zero crossing without interference from remote activity or repolarization waves. Its amplitude increased with decreasing interelectrode distance. Following epicardial stimulation, Laplacian amplitude was significantly larger than during a breakthrough pattern. During VF, identical unipolar electrograms corresponded to Laplacian complexes with different morphology. Collision of wavefronts was associated with entirely positive Laplacian waveforms; "focal" appearance of activity was associated with an entirely negative waveform. Activation block in the activation maps was correlated with the appearance of sustained episodes of negativity or positivity in the Laplacian electrogram (depending on the location of the recording site relative to the line of block). CONCLUSION: Laplacian electrograms allow detection of the moment of local activation without interference from remote activity or repolarization, especially during complex arrhythmias. The technique applied to automatic sensing devices, such as the internal defibrillator, may optimize defibrillation success.

Action Potentials↗

Spatial filtering methods for local activation determination in fractionated electrograms from simulated infarcted hearts.

The purpose of this work is the enhancement of local activation in multiphasic extracellular recordings coming from infarcted myocardial tissue and, consequently, the distinction of local from distal activation. Deconvolution procedures are applied, in the form of spatial filtering, in order to estimate transmembrane currents from the extracellular recordings. Simulated data are used in order to test the methods. The current source estimates are compared to the actual transmembrane currents and to Laplacian estimates.

Computer Simulation↗

Effects of intracavitary blood flow and electrode-target distance on radiofrequency power required for transient conduction block in a Langendorff-perfused canine model.

OBJECTIVES: We sought to quantify the effects of electrode-target distance and intracavitary blood flow on radiofrequency (RF) power required to induce transient conduction block, using a Langendorff-perfused canine ablation model. BACKGROUND: Given the thermally mediated nature of RF catheter ablation, cooling effects of intracavitary blood flow and electrode-target distance will influence lesion extension and geometry and electrophysiologic effects. METHODS: In eight Langendorff-perfused canine hearts, the right ventricular free wall was opened, and the right bundle branch (RBB) carefully localized by multielectrode activation mapping. The right atrium was paced at cycle length of 500 ms. Proximal and distal electrodes were attached at the endocardial aspect of the RBB, and the perfused heart was submerged in heparinized blood at 37 degrees C. A standard 4-mm tip ablation electrode was positioned at a constant contact pressure of 5 g between the two electrodes at the site of maximal RBB potential (0 mm) and 2 and 4 mm distant from this site along a line perpendicular to the RBB. RF pulses (500 kHz) were delivered for 30 s at 0.5-W increments until transient bundle branch block. In four hearts, intracavitary flow was simulated by directing a 30-cm/s jet of blood parallel to the septum at the ablation site, and the protocol was repeated to assess the effects on power required for block. In one heart, the effect of variable flow was assessed (0, 15 and 30 cm/s). RESULTS: An exponential distance-related increase was seen in power required for block, from 1.8 +/- 0.9 W (mean +/- SD) at 0 mm to 5.4 +/- 1.1 W at 4 mm. In the presence of 30-cm/s flow, an increase to 3.9 +/- 0.8 W at 0 mm and 13.1 +/- 2.4 W at 2 mm was seen. At 4 mm, coagulum formation invariably occurred before block could be induced. For 15-cm/s flow, less power was required: 3 and 7 W at 0 and 2 mm, respectively. CONCLUSIONS: Increasing the ablation electrode-target distance causes an exponential increase in power required for conduction block; this relation is profoundly influenced by intracavitary flow. Given the geometry of endomyocardial RF lesions, these findings are particularly relevant for directly subendocardial ablation targets.

Animals↗

Cost-effectiveness of implantable defibrillator as first-choice therapy versus electrophysiologically guided, tiered strategy in postinfarct sudden death survivors. A randomized study.

BACKGROUND: Rising costs of health care, partly as a result of costly therapeutic innovations, are of concern to both the medical profession and healthcare authorities. The implantable cardioverter-defibrillator (ICD) is still not remunerated by Dutch healthcare insurers. The aim of this study was to evaluate the cost-effectiveness of early implantation of the ICD in postinfarct sudden death survivors. METHODS AND RESULTS: Sixty consecutive postinfarct survivors of cardiac arrest caused by ventricular tachycardia or fibrillation were randomly assigned either ICD as first choice (n = 29) or a tiered therapy starting with antiarrhythmic drugs and guided by electrophysiological (EP) testing (n = 31). Median follow-up was 729 days (range, 3 to 1675 days). Fifteen patients died, 4 in the early ICD group and 11 in the EP-guided strategy group (P = .07). For quantitative assessment, the cost-effectiveness ratio was calculated for both groups and expressed as median total costs per patient per day alive. Because effectiveness aspects other than mortality are not incorporated in this ratio, other factors related to quality of life were used as qualitative measures of cost-effectiveness. The cost-effectiveness ratios were $63 and $94 for the early ICD and EP-guided strategy groups, respectively, per patient per day alive. This amounts to a net cost-effectiveness of $11,315 per patient per year alive saved by early ICD implantation. Costs in the early ICD group were higher only during the first 3 months of follow-up, but as a result of the high proportion of therapy changes, including arrhythmia surgery and late ICD implantation, costs in the EP-guided strategy group became higher after that. Patients discharged with antiarrhythmic drugs as sole therapy had the lowest total costs. This subset, however, showed extremely high mortality, resulting in a poor cost-effectiveness ratio ($196 per day). Invasive therapies and hospitalization were the major contributors to costs. If quality-of-life measures are taken into account, the cost-effectiveness of early ICD implantation was even more favorable. Recurrent cardiac arrest and cardiac transplantation occurred in the EP-guided strategy group only, whereas exercise tolerance, total hospitalization duration, number of invasive procedures, and antiarrhythmic therapy changes were significantly in favor of early ICD implantation. CONCLUSIONS: In terms of cost-effectiveness, early ICD implantation is superior to the EP-guided therapeutic strategy in postinfarct sudden death survivors.

Anti-Arrhythmia Agents↗

Fractionated electrograms in dilated cardiomyopathy: origin and relation to abnormal conduction.

OBJECTIVES: We sought to investigate the origin of the fractionated electrogram and its relations to abnormal conduction in cardiomyopathic myocardium. BACKGROUND: Patients with dilated cardiomyopathy have a high incidence of ventricular tachycardias. Electrograms recorded in these patients are often fractionated. METHODS: High resolution mapping (200-microM interelectrode distance) of the electrical activity was carried out in 11 superfused papillary muscles and 6 trabeculae from 7 patients who underwent heart transplantation because of dilated cardiomyopathy. Similar measurements were taken in four papillary muscles from dog hearts in which electrical barriers had been artificially made. Ten human preparations were studied histologically. RESULTS: All preparations revealed sites with fractionated electrograms. In three human preparations, activation patterns showed a discernible line of activation block running parallel to the fiber direction. Fractionated electrograms were recorded at sites contiguous to the line of block. In five preparations, fractionated electrograms were recorded at sites where lines of block were not identified. In these preparations, electrical barriers consisted of short stretches of fibrous tissue. In the remaining nine preparations, fractionated electrograms were recorded, both from sites contiguous to distinct obstacles and sites without evidence of a barrier. CONCLUSIONS: Our observations showed that fractionated electrograms recorded in myocardium damaged by cardiomyopathy were due to both distinct, long strands and short stretches of fibrous tissue. Delayed conduction was caused by curvation of activation around the distinct lines of block and by the wavy course of activation between the short barriers. The latter reflects extreme nonuniform anisotropy.

Animals↗

Increase in hospital admission rates for heart failure in The Netherlands, 1980-1993.

OBJECTIVE: To study the trend in hospital admission rates for heart failure in the Netherlands from 1980 to 1993. DESIGN: All hospital admissions in the Netherlands with a principal discharge diagnosis of heart failure were analysed. In addition, individual records of heart failure patients from a subset of 7 hospitals were analysed to estimate the frequency and timing of readmissions. RESULTS: The total number of discharges for men increased from 7377 in 1980 to 13 022 in 1993, and for women from 7064 to 12 944. From 1980 through 1993 age adjusted discharge rates rose 48% for men and 40% for women. Age adjusted in-hospital mortality for heart failure decreased from 19% in 1980 to 15% in 1993. For all age groups in-hospital mortality for men was higher than for women. The mean length of hospital admissions in 1993 was 14.0 days for men and 16.4 days for women. A review of individual patient records from a 6.3% sample of all hospital admissions in the Netherlands indicated that within a 2 year period 18% of the heart failure patients were admitted more than once and 5% more than twice. CONCLUSIONS: For both men and women a pronounced increase in age adjusted discharge rates for heart failure was observed in the Netherlands from 1980 to 1993. Readmissions were a prominent feature among heart failure patients. Higher survival rates after acute myocardial infarction and the longer survival of patients with heart disease, including heart failure may have contributed to the observed increase. The importance of advances in diagnostic tools and of possible changes in admission policy remain uncertain.

Age Distribution↗

Dispersion of 'refractoriness' in noninfarcted myocardium of patients with ventricular tachycardia or ventricular fibrillation after myocardial infarction.

BACKGROUND: Postinfarction ventricular tachycardias (VTs) may degenerate into ventricular fibrillation (VF), but this does not happen in all patients. The underlying mechanism is not exactly known, but dispersion of refractory periods is considered a major factor in both induction and persistence of reentrant arrhythmias in general. Hypertrophied, noninfarcted myocardium has altered electrophysiological characteristics. We hypothesized that noninfarcted ventricular tissue may provide the heterogeneities that cause the transition from VT into VF. Local fibrillation intervals, ie, the average interval between local activations during VF, have previously been shown to correlate well with local refractoriness in human and canine atrium and in porcine and canine ventricle and may therefore be used as an index of local refractoriness. This technique permits simultaneous assessment of refractoriness at multiple sites. METHODS AND RESULTS: We measured local fibrillation intervals at 32 to 64 sites in the noninfarcted part of the left ventricle in patients undergoing antiarrhythmic surgery for symptomatic, drug-refractory, postinfarction ventricular tachyarrhythmias. The grid of electrodes (interelectrode distance, 7 mm) was attached to the epicardium of the left ventricle remote from the infarcted tissue. Group 1 consisted of 7 patients with hemodynamically tolerable sustained VT (VT group). Group 2 consisted of 7 patients with cardiac arrest and documented VF (VF group). With the patients on cardiopulmonary bypass, VF was induced by multiple premature stimulation. The VF interval was not significantly different in the two study groups (VT group, 136 +/- 5.5 ms; VF group, 129 +/- 3.4 ms, mean +/- SEM). However, spatial dispersion of the VF intervals (remote from the infarcted area) expressed as the coefficient of variation of VF intervals (SD x 100/mean VF interval in each heart) was significantly larger in the VF group. It was 3.63 +/- 0.56 in the VF group and 1.55 +/- 0.40 in the VT group (mean +/- SEM; P < .01). Differences between the shortest and longest VF intervals in one and the same heart and the largest difference between two adjacent sites were also larger in the VF group (P < .02 and P < .05, respectively). CONCLUSIONS: This study shows larger dispersion in VF intervals and therefore suggests larger dispersion of refractory periods in parts of the myocardium remote from the infarction in patients with postinfarction VF than in patients with postinfarction VT.

Aged↗

Effects of barriers on propagation of action potentials in two-dimensional cardiac tissue. A computer simulation study.

A two-dimensional anisotropic model of cardiac ventricular muscle was used to study the effects of discontinuities (barriers), such as dead cells or high-resistance areas, on longitudinal plane-wave propagation. Problems in propagation appear when long barriers become thicker and their spacing closer. Short barriers with large widths and small spacing also cause propagation disturbances and significant delays in their vicinity. If the plane wave front propagates through the barriers, the velocity returns to near normal within one-length constant away from the end of the barrier region. For a funnel-like structure, an opening of 13 cells should exist for longitudinal plane wave propagation. For smaller openings, the ratio of openings required for propagation to occur when traveling from a narrow to a wider area of tissue is proportional to the anisotropy ratio, which can cause unidirectional block. Tortuosity, created by spatial distribution of dead cell barriers, can facilitate propagation by changing the effective impedance the wave front sees, and can create multiple local delays, which may result in discrepancies when measuring propagation velocity.

Action Potentials↗

[Increase in the number of admissions due to heart failure in Dutch hospitals in the period 1980-1992].

OBJECTIVE: Determination of the trend in the occurrence of hospital admissions because of heart failure in the Netherlands. DESIGN: Descriptive investigation. SETTING: Dutch general and university hospitals. METHOD: Data on hospital admissions because of heart failure from 1980 to 1992, obtained from the National Medical Register, were analysed. Three ICD-9 CM diagnoses were combined (congestive heart failure 428.x, diseases of the heart due to hypertension 402.x and myocardial degeneration 429.I). RESULTS: From 1980 through 1992 the annual number of hospital admissions for heart failure increased by 69%, for both men and women, from 14,441 to 24,368. Age-adjusted admission rates increased by 43% for men, and by 30% for women. The admission rates were strongly age-related, with higher rates in the older age groups. Among men 89% of the patients in 1992 were older than 60 years, and 63% older than 70 years. Among women these figures were 94% and 79%, respectively. During the study period the age-specific admission rates rose in all relevant age groups. The rise was higher in the older age groups. In 1992 the average duration of stay in hospital was 14 days for men and 17 for women. CONCLUSION: Probable causes of the rise in the number of hospital admissions for heart failure were the increasing median age of the population, higher survival rates after acute myocardial infarction and longer survival of persons with heart disease. Demographic changes and medical progress will probably lead to a further rise in morbidity and mortality and of costs of heart failure.

Academic Medical Centers↗

Dispersion of refractoriness in normal and ischaemic canine ventricle: effects of sympathetic stimulation.

OBJECTIVE: Dispersion in refractoriness is considered a major factor in induction and persistence of cardiac arrhythmias. The sympathetic nervous system is known to modulate refractoriness. An index of refractoriness has therefore been assessed in normal and ischaemic myocardium simultaneously at multiple sites, with and without sympathetic stimulation. METHODS: In six dogs on total cardiopulmonary bypass the average interval between local activations was measured during artificially induced ventricular fibrillation from extracellular electrograms simultaneously recorded from 32 ventricular sites. These local ventricular fibrillation intervals may be used as an index of local refractoriness. RESULTS: During regional ischaemia, ventricular fibrillation intervals of ischaemic sites could prolong by up to 60% after 3 min following coronary occlusion. Left stellate ganglion stimulation during ischaemia produced either no response or prolonged the ventricular fibrillation intervals even further at ischaemic sites, whereas ventricular fibrillation intervals at non-ischaemic sites shortened. Dispersion in refractoriness across the ischaemic border increased by 14-59% in individual hearts following sympathetic stimulation during acute, regional ischaemia. CONCLUSIONS: Due to opposite effects on normal and ischaemic myocardium, sympathetic stimulation increases the difference in refractoriness over the ischaemic border. This may enhance the chance for regional conduction block and the propensity to re-entrant arrhythmias.

Acute Disease↗

Interaction of sympathetic and parasympathetic nervous system on ventricular refractoriness assessed by local fibrillation intervals in the canine heart.

OBJECTIVE: The aim was to assess the effects of autonomic nerve stimulation on local ventricular refractoriness by measuring local ventricular fibrillation intervals. METHODS: In 10 dogs on cardiopulmonary bypass, ventricular fibrillation intervals were recorded simultaneously at up to 32 sites before and after neural stimulation. In four dogs (group 1) the response to bilateral stellate ganglion stimulation was measured before and after bilateral cervical vagotomy. In three dogs (group 2) bilateral stellate ganglion stimulation, vagal nerve stimulation, and combined vagal and stellate ganglia stimulation were performed. In three dogs (group 3) the same protocol was applied after total decentralisation of the autonomic nervous system. RESULTS: Bilateral stellate ganglion stimulation shortened the ventricular fibrillation interval at 44-50% of myocardial sites before and after vagotomy, whereas prolongation of the interval was observed at 14-18% of the sites. At higher stimulus strength shortening of the interval was measured at 85% of the sites in the intact and decentralised groups. No prolongation was observed. The shortening was largest in the decentralised group (11.1 ms). Dispersion in refractoriness increased in hearts from all groups, but not in each individual heart. Left, right, or bilateral vagal stimulation was without effect at about 75% of the tested sites. The fact that the response to autonomic nerve stimulation varies from site to site warrants our approach of simultaneous recordings at multiple sites. Dispersion in refractoriness was not affected by vagal stimulation. Combined autonomic stimulation had approximately the same effect on dispersion in refractoriness as bilateral stellate ganglion stimulation alone. However, vagal stimulation attenuated the responses to bilateral stellate ganglion stimulation by some 20% in the decentralised group. CONCLUSIONS: Vagal stimulation has minor effects on ventricular refractoriness, but this is not due to sparse innervation, since vagal stimulation is able to mitigate the effects of sympathetic stimulation in decentralised hearts.

Animals↗

Slow conduction in the infarcted human heart. 'Zigzag' course of activation.

BACKGROUND: Ventricular tachycardias occurring in the chronic phase of myocardial infarction are caused by reentry. Areas of slow conduction, facilitating reentry, are often found in the infarcted zone. The purpose of this study was to elucidate the mechanism of slow conduction in the chronic infarcted human heart. METHODS AND RESULTS: Spread of activation was studied in infarcted papillary muscles from hearts of patients who underwent heart transplantation because of infarction. Recordings were carried out on 10 papillary muscles that were superfused in a tissue bath. High-resolution mapping was performed in areas revealing slow conduction. Activation delay between sites perpendicular to the fiber direction and 1.4 mm apart could be as long as 45 milliseconds. Analysis of activation times revealed that activation spread in tracts parallel to the fiber direction. Conduction velocity in the tracts was between 0.6 and 1 m/s. Although tracts were separated from each other over distances up to 8 mm, they often connected with each other at one or more sites, forming a complex network of connected tracts. In this network, wave fronts could travel perpendicular to the fiber direction. Separation of tracts was due to collagenous septa. At sites where tracts were interconnected, the collagenous barriers were interrupted. CONCLUSIONS: Slow conduction perpendicular to the fiber direction in infarcted myocardial tissue is caused by a "zigzag" course of activation at high speed. Activation proceeds along pathways lengthened by branching and merging bundles of surviving myocytes ensheathed by collagenous septa.

Electrocardiography↗

Increased dispersion of "refractoriness" in patients with idiopathic paroxysmal atrial fibrillation.

The average interval between local depolarizations during atrial fibrillation, the so-called atrial fibrillation interval, was used as an index for local "refractoriness." This was based on the assumption that during fibrillation, cells are reexcited as soon as their refractory period ends. A very good correlation was found between refractory periods determined with the extrastimulus technique at a basic cycle length of 400 ms and atrial fibrillation intervals measured at the same epicardial sites of the right atrium. This new technique was used to assess dispersion in atrial fibrillation intervals in 10 patients with idiopathic paroxysmal atrial fibrillation and in a control group of 6 patients who were undergoing cardiac surgery. After a routine median sternotomy a multiterminal grid with up to 40 electrodes was placed over the right atrium, and atrial fibrillation was induced by premature stimulation. The average fibrillation interval in the test group, recorded at 247 sites, was 152 +/- 3 ms and that in the control group, recorded at 118 sites, was 176 +/- 8.1 ms (p less than 0.05). Dispersion in atrial fibrillation intervals, defined as the variance of the fibrillation intervals at all the recording sites, was three times larger in the group with paroxysmal atrial fibrillation than in the control group. This study suggests that both a shorter refractory period and a larger dispersion in refractoriness are responsible for the recurrence of atrial fibrillation.

Atrial Fibrillation↗

Macroreentry in the infarcted human heart: the mechanism of ventricular tachycardias with a "focal" activation pattern.

Endocardial mapping of electrical activity was carried out in 150 patients to guide antiarrhythmic surgery for drug-resistant ventricular tachycardia in the chronic phase of myocardial infarction. In 20 of these patients, the activation pattern of 27 distinct tachycardias was focal and diastolic potentials were recorded at three or more sites. In 26 tachycardias, the sequence of diastolic potentials progressed from the area of latest activation of one cycle toward the "origin" of the next cycle. In two patients, the heart was stimulated during tachycardia, resulting in entrainment of the tachycardia in both. Late potentials were recorded during entrainment at sites where diastolic potentials occurred during tachycardia. In 11 of the 20 patients, endocardial mapping was performed during sinus rhythm. In four of these, late potentials were observed during sinus rhythm at sites where diastolic potentials were recorded during tachycardia. In two patients without late potentials during sinus rhythm, late potentials were observed during stimulation and induced ectopic beats. The results support the concept that the mechanism of several of these tachycardias is based on reentry in a macrocircuit comprising a tract of surviving tissue traversing the infarct and the remaining healthy tissue. They also indicate that the absence of late potentials during sinus rhythm does not guarantee the absence of arrhythmogenic pathways.

Cardiac Catheterization↗

Dispersion of refractoriness in canine ventricular myocardium. Effects of sympathetic stimulation.

In 18 dogs on total cardiopulmonary bypass, the average interval between local activations during artificially induced ventricular fibrillation (VF interval) was measured from extracellular electrograms, simultaneously recorded from up to 32 ventricular sites. VF intervals were used as an index of local refractoriness, based on the assumption that during ventricular fibrillation, cells are reexcited as soon as they have recovered their excitability. In support of this, microelectrode recordings in two hearts during ventricular fibrillation did not show a diastolic interval between successive action potentials. Refractory periods determined at a basic cycle length of 300 msec with the extrastimulus method correlated well with VF intervals measured at the same sites. Thus, this technique allows assessment of spatial dispersion of refractoriness during brief interventions such as sympathetic stimulation. The responses to left, right, and combined stellate ganglion stimulation varied substantially among individual hearts. This was observed both in dogs with an intact (n = 12) and decentralized (n = 6) autonomic nervous system. Individual ventricular sites could show effects of both left and right stellate ganglion stimulation (42% of tested sites) or show effects of left-sided stimulation only (31%) or right-sided stimulation only (14%). In 13% of sites, no effects of stellate stimulation were observed. Apart from these regional effects, the responses could be qualitatively different; that is, within the same heart, the VF interval prolonged at one site but shortened at another in response to the same intervention, although shortening was the general effect and prolongation the exception. Whenever sites responded to stellate ganglion stimulation with a shortening of VF interval, this shortening was approximately 10% for left, right, or combined stimulation, whether the autonomic nervous system was intact or decentralized. In six of 12 hearts in the intact group, there was a distinct regional effect of left stellate ganglion stimulation; in the other six hearts, the effects were distributed homogeneously over the ventricles. In three hearts, the effect of left stellate ganglion stimulation was strongest in the posterior wall, and in the other three hearts, in the anterior wall. The effects of right stellate ganglion stimulation were restricted to the anterior or lateral part of the left ventricle. Dispersion of VF intervals increased after left and combined stellate ganglion stimulation in the intact group and after right stellate ganglion stimulation in the decentralized group, but not significantly in every heart. This points to a marked individual variation with regard to the effects of sympathetic stimulation on electrophysiological properties of the heart.

Action Potentials↗

Injury current and gradients of diastolic stimulation threshold, TQ potential, and extracellular potassium concentration during acute regional ischemia in the isolated perfused pig heart.

During acute regional myocardial ischemia, a "current of injury" flows between the ischemic and the normal tissue. Its direction and magnitude change during the cardiac cycle. During diastole, the injury current flows intracellularly from the ischemic cells toward the normal cells and tends to depolarize the latter. The gain insight into the possible role of the injury current in arrhythmogenesis, we simultaneously determined diastolic stimulation threshold, [K+]o and TQ potential at multiple sites closely spaced across the cyanotic border in Langendorff-perfused pig hearts during the first 10 minutes after occlusion of the left anterior descending coronary artery. The position of the electrodes relative to the border was validated by their response to 1) regional ischemia and 2) selective perfusion with a high-K+ perfusate of the left anterior descending coronary artery. A temporary decrease of diastolic stimulation threshold preceded a rapid increase in the central ischemic zone; a lasting reduction (by +/- 20%) without a concomitant increase of [K+]o was observed at seven sites (of 39 sites tested), five of which were less than 2 mm outside the electrophysiological border. Moreover, up to 4 mm inside the electrophysiological border, a similar lasting decrease of diastolic stimulation threshold was accompanied by a moderate increase of [K+]o. We conclude that 1) the injury current causes increased excitability in normal tissue close to the "ischemic" border and 2) increased excitability related to a moderately increased [K+]o may persist up to 10 minutes of ischemia at the ischemic side of the border. Both factors may facilitate the induction of life-threatening arrhythmias in acute myocardial ischemia.

Action Potentials↗

Platelet hyperreactivity and prognosis in survivors of myocardial infarction.

We tested the hypothesis that an increase in spontaneous aggregability of platelets in vitro predicts mortality and coronary events in patients who have survived a recent myocardial infarction. A cohort of 149 survivors of infarction entered our study three months after the index infarction and was followed for five years. At entry and at intervals of six months, spontaneous platelet aggregation (SPA) was tested and graded as positive (aggregation within 10 minutes), intermediate (aggregation after 10 to 20 minutes), or negative (no aggregation within 20 minutes). During follow-up, 6.4 percent (6 of 94) of the patients in the SPA-negative group died, as compared with 10.3 percent (3 of 29) in the SPA-intermediate group and 34.6 percent (9 of 26) in the SPA-positive group. As compared with the SPA-negative group, the SPA-intermediate group had a relative risk of death of 1.6 (95 percent confidence interval, 0.5 to 5.5) and the SPA-positive group had a risk of 5.4 (95 percent confidence interval, 2.2 to 13.4). At least one cardiac event (cardiac death or recurrent nonfatal myocardial infarction) occurred in 14.9 percent (14 of 94 patients) of the SPA-negative group, 24.1 percent (7 of 29) of the SPA-intermediate group, and 46.2 percent (12 of 26) of the SPA-positive group. A positive test result continued to have prognostic value throughout the five-year study. We conclude that spontaneous platelet aggregation in vitro is a useful biologic marker for the prediction of coronary events and mortality in this low-risk group of survivors of a myocardial infarction. A causal relation is suggested but not proved by our study.

Biomarkers↗