Myocardial Electrical Impedance Research Articles

Endocardial infarct scar recognition by myocardial electrical impedance is not influenced by changes in cardiac activation sequence

Measurement of myocardial electrical impedance can allow recognition of infarct scar and is theoretically not influenced by changes in cardiac activation sequence, but this is not known. The objectives of this study were to evaluate the ability of endocardial electrical impedance measurements to recognize areas of infarct scar and to assess the stability of the impedance data under changes in cardiac activation sequence. One-month-old myocardial infarction confirmed by cardiac magnetic resonance imaging was induced in 5 pigs submitted to coronary artery catheter balloon occlusion. Electroanatomic data and local electrical impedance (magnitude, phase angle, and amplitude of the systolic-diastolic impedance curve) were recorded at multiple endocardial sites in sinus rhythm and during right ventricular pacing. By merging the cardiac magnetic resonance and electroanatomic data, we classified each impedance measurement site either as healthy (bipolar amplitude ≥1.5 mV and maximum pixel intensity <40%) or scar (bipolar amplitude <1.5 mV and maximum pixel intensity ≥40%). A total of 137 endocardial sites were studied. Compared to healthy tissue, areas of infarct scar showed 37.4% reduction in impedance magnitude (P < .001) and 21.5% decrease in phase angle (P < .001). The best predictive ability to detect infarct scar was achieved by the combination of the 4 impedance parameters (area under the receiver operating characteristic curve 0.96; 95% confidence interval 0.92-1.00). In contrast to voltage mapping, right ventricular pacing did not significantly modify the impedance data. Endocardial catheter measurement of electrical impedance can identify infarct scar regions, and in contrast to voltage mapping, the impedance data are not affected by changes in cardiac activation sequence.

Normothermic Ex Vivo Heart Perfusion: Effects of Live Animal Blood and Plasma Cross Circulation.

Prolonged normothermic ex vivo heart perfusion could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via normothermic ex vivo heart perfusion. Standard perfusion (SP; n = 40) utilized red blood cell/plasma perfusate and Langendorff technique for a goal of 12 hours. Cross-circulation groups used a similar circuit with the addition of cross-circulated venous whole blood (XC-blood; n = 6) or cross-circulated filtered plasma (XC-plasma; n = 7) between a live paracorporeal pig under anesthesia and the perfusate reservoir. Data included oxygen metabolism, vascular resistance, lactate production, left ventricular function, myocardial electrical impedance, and histopathologic injury score. All cross-circulation hearts were successfully perfused for 12 hours, compared with 22 of 40 SP hearts (55%; p = 0.002). Both cross-circulation groups demonstrated higher oxygen consumption and vascular resistance than standard hearts from hours 3-12. No significant differences were seen between XC-blood and XC-plasma hearts in any variable, including left ventricular dP/dT after 12 hours (1478 ± 700 mm Hg/s vs. 872 ± 500; p = 0.17). We conclude that cross circulation of whole blood or plasma from a live animal improves preservation of function of perfused hearts, and cross-circulated plasma performs similarly to cross-circulated whole blood.

Recognition of Fibrotic Infarct Density by the Pattern of Local Systolic-Diastolic Myocardial Electrical Impedance

Myocardial electrical impedance is a biophysical property of the heart that is influenced by the intrinsic structural characteristics of the tissue. Therefore, the structural derangements elicited in a chronic myocardial infarction should cause specific changes in the local systolic-diastolic myocardial impedance, but this is not known. This study aimed to characterize the local changes of systolic-diastolic myocardial impedance in a healed myocardial infarction model. Six pigs were successfully submitted to 150 min of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 4 weeks later, myocardial impedance spectroscopy (1–1000 kHz) was measured at different infarction sites. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow (ABF) were also recorded. A total of 59 LV tissue samples were obtained and histopathological studies were performed to quantify the percentage of fibrosis. Samples were categorized as normal myocardium (<10% fibrosis), heterogeneous scar (10–50%) and dense scar (>50%). Resistivity of normal myocardium depicted phasic changes during the cardiac cycle and its amplitude markedly decreased in dense scar (18 ± 2 Ω·cm vs. 10 ± 1 Ω·cm, at 41 kHz; P < 0.001, respectively). The mean phasic resistivity decreased progressively from normal to heterogeneous and dense scar regions (285 ± 10 Ω·cm, 225 ± 25 Ω·cm, and 162 ± 6 Ω·cm, at 41 kHz; P < 0.001 respectively). Moreover, myocardial resistivity and phase angle correlated significantly with the degree of local fibrosis (resistivity: r = 0.86 at 1 kHz, P < 0.001; phase angle: r = 0.84 at 41 kHz, P < 0.001). Myocardial infarcted regions with greater fibrotic content show lower mean impedance values and more depressed systolic-diastolic dynamic impedance changes. In conclusion, this study reveals that differences in the degree of myocardial fibrosis can be detected in vivo by local measurement of phasic systolic-diastolic bioimpedance spectrum. Once this new bioimpedance method could be used via a catheter-based device, it would be of potential clinical applicability for the recognition of fibrotic tissue to guide the ablation of atrial or ventricular arrhythmias.

Physical Justification of an Increase in the Efficacy of Radiofrequency Systems for Myocardial Ablation

The article presents data on dependence of the myocardial electrical impedance on the temperature. These data have high clinical relevance because radio frequency energy-induced destruction of the myocardium in the course of surgical treatment of cardiac arrhythmias should be performed transmurally. Insufficient transmural myocardial damage results in recurrence of cardiac arrhythmias. Therefore, achieving transmural treatments of the myocardium is of high significance.Studies were performed by using 20 isolated hearts. To evaluate the effectiveness of radio frequency exposure, we studied two temperature settings: myocardial normothermia (36.6 °C) and myocardial hypothermia (20 °C). The depth of destruction as well as the temperatures of the epicardial, endocardial, and intramural myocardium at the points of impact were estimated. Data showed that lower temperature decreases tissue electrical impedance and results in a greater depth of damage.

Early detection of acute transmural myocardial ischemia by the phasic systolic-diastolic changes of local tissue electrical impedance.

Myocardial electrical impedance is influenced by the mechanical activity of the heart. Therefore, the ischemia-induced mechanical dysfunction may cause specific changes in the systolic-diastolic pattern of myocardial impedance, but this is not known. This study aimed to analyze the phasic changes of myocardial resistivity in normal and ischemic conditions. Myocardial resistivity was measured continuously during the cardiac cycle using 26 different simultaneous excitation frequencies (1 kHz-1 MHz) in 7 anesthetized open-chest pigs. Animals were submitted to 30 min regional ischemia by acute left anterior descending coronary artery occlusion. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow were recorded simultaneously. Baseline myocardial resistivity depicted a phasic pattern during the cardiac cycle with higher values at the preejection period (4.19 ± 1.09% increase above the mean, P < 0.001) and lower values during relaxation phase (5.01 ± 0.85% below the mean, P < 0.001). Acute coronary occlusion induced two effects on the phasic resistivity curve: 1) a prompt (5 min ischemia) holosystolic resistivity rise leading to a bell-shaped waveform and to a reduction of the area under the LV pressure-impedance curve (1,427 ± 335 vs. 757 ± 266 Ω·cm·mmHg, P < 0.01, 41 kHz) and 2) a subsequent (5-10 min ischemia) progressive mean resistivity rise (325 ± 23 vs. 438 ± 37 Ω·cm at 30 min, P < 0.01, 1 kHz). The structural and mechanical myocardial dysfunction induced by acute coronary occlusion can be recognized by specific changes in the systolic-diastolic myocardial resistivity curve. Therefore these changes may become a new indicator (surrogate) of evolving acute myocardial ischemia.

Editorial: Cardiac electronic remodeling and susceptibility to arrhythmias: an introduction and brief historical overview.

Editorial: Cardiac electronic remodeling and susceptibility to arrhythmias: an introduction and brief historical overview.

Myocardial electrotonic response to submaximal exercise in dogs with healed myocardial infarctions: evidence for β-adrenoceptor mediated enhanced coupling during exercise testing.

Introduction: Autonomic neural activation during cardiac stress testing is an established risk-stratification tool in post-myocardial infarction (MI) patients. However, autonomic activation can also modulate myocardial electrotonic coupling, a known factor to contribute to the genesis of arrhythmias. The present study tested the hypothesis that exercise-induced autonomic neural activation modulates electrotonic coupling (as measured by myocardial electrical impedance, MEI) in post-MI animals shown to be susceptible or resistant to ventricular fibrillation (VF).Methods: Dogs (n = 25) with healed MI instrumented for MEI measurements were trained to run on a treadmill and classified based on their susceptibility to VF (12 susceptible, 9 resistant). MEI and ECGs were recorded during 6-stage exercise tests (18 min/test; peak: 6.4 km/h @ 16%) performed under control conditions, and following complete β-adrenoceptor (β-AR) blockade (propranolol); MEI was also measured at rest during escalating β-AR stimulation (isoproterenol) or overdrive-pacing.Results: Exercise progressively increased heart rate (HR) and reduced heart rate variability (HRV). In parallel, MEI decreased gradually (enhanced electrotonic coupling) with exercise; at peak exercise, MEI was reduced by 5.3 ± 0.4% (or -23 ± 1.8Ω, P < 0.001). Notably, exercise-mediated electrotonic changes were linearly predicted by the degree of autonomic activation, as indicated by changes in either HR or in HRV (P < 0.001). Indeed, β-AR blockade attenuated the MEI response to exercise while direct β-AR stimulation (at rest) triggered MEI decreases comparable to those observed during exercise; ventricular pacing had no significant effects on MEI. Finally, animals prone to VF had a significantly larger MEI response to exercise.Conclusions: These data suggest that β-AR activation during exercise can acutely enhance electrotonic coupling in the myocardium, particularly in dogs susceptible to ischemia-induced VF.

Myocardial electrical activity does not affect myocardial electrical impedance measurements

Myocardial electrical impedance (MEI) has shown to be an effective indicator of myocardial ischemia. We have previously developed a novel monitor for measuring MEI in near-real time. The object of this study was to test whether drug-induced changes in the frequency of the periodic myocardial electrical activity, as measured by the heart rate (HR), affect MEI measurements made with our monitor. Thirty dogs were randomly assigned to one of three study groups (placebo, isoproterenol or esmolol) and then anesthetized with sodium thiamylal, intubated, ventilated, given isoflurane, and had venous, arterial, and pulmonary artery catheters placed. Median sternotomy was performed to facilitate myocardial exposure and to allow the left anterior descending (LAD) coronary artery to be isolated. Following baseline measurements, saline (control), isoproterenol or esmolol was administered and the LAD coronary artery was occluded in a timed sequence in order to study the effects of heart rate changes and demonstrate induced myocardial ischemia on MEI. Isoproterenol raised the HR and esmolol lowered the HR without affecting our MEI measurements. Myocardial electrical impedance increased during LAD coronary artery occlusion in all groups, as previously shown. These results demonstrate that our MEI monitor is unaffected by the frequency of the periodic myocardial electrical activity that generates the HR.

Myocardial electrical impedance as a predictor of the quality of RF-induced linear lesions

Production of complete (i.e. continuous and transmural) cardiac lesions by radiofrequency (RF) ablation can cure certain cardiac arrhythmias. However, a predictor of lesion completeness that is reliable and can be measured intraoperatively is needed in order to maximize effectiveness of ablation therapy. Predictors that require membrane excitation or response to stimulation are not always practical. This study tested whether changes of myocardial impedance across the lesion can predict completeness. RF energy was applied epicardially on perfused rabbit ventricles to produce linear lesions that were complete (n = 25) or incomplete (noncontinuous or nontransmural, n = 25). Before and after creation of each lesion, the magnitude and phase of impedance at 1 kHz were measured with a four-electrode epicardial array across the lesion. For 16 of the lesions, the translesion stimulus-excitation delay was also measured. Lesion completeness was evaluated with 2,3,5-triphenyltetrazolium chloride stain. Complete lesions increased resistivity by 26 Ω cm (21% of the preablation value, p = 0.0007, n = 17) when the inactive RF electrode remained on the epicardium during impedance measurements. When the RF electrode was removed during measurements, the rise of resistivity by complete lesions increased to 58 Ω cm (30% of the preablation value, p = 0.022, n = 8). For incomplete lesions, resistivity did not change significantly. Ablation did not significantly alter the phase of impedance. Accuracies of predictions of lesion completeness by the change in resistivity or the change in translesion stimulus-excitation delay were comparable (Youden's index 0.75 and 0.625, respectively, n = 16). Thus, RF ablation increases myocardial resistivity. The resistivity can predict lesion completeness and may provide an alternative to predictors based on excitation.

Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate‐mediated attenuation

Parasympathetic activity during acute coronary artery occlusion (CAO) can protect against ischaemia-induced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear. During CAO, myocardial electrotonic uncoupling is associated with autonomically mediated immediate (i.e. type 1A) arrhythmias and can modulate pro-arrhythmic dispersion of repolarization. Therefore, the effects of acutely enhanced or decreased cardiac parasympathetic activity on early electrotonic coupling during CAO, as measured by myocardial electrical impedance (MEI), were investigated. Anaesthetized dogs were instrumented for MEI measurements, and left circumflex coronary arterial occlusions were performed in intact (CTRL) and vagotomized (VAG) animals. The CAO was followed by either vagotomy (CTRL) or vagal nerve stimulation (VNS, 10 Hz, 10 V) in the VAG dogs. Vagal nerve stimulation was studied in two additional sets of animals. In one set heart rate (HR) was maintained by pacing (220 beats min(-1)), while in the other set bilateral stellectomy preceded CAO. The MEI increased after CAO in all animals. A larger MEI increase was observed in vagotomized animals (+85 +/- 9 Omega, from 611 +/- 24 Omega, n = 16) when compared with intact control dogs (+43 +/- 5 Omega, from 620 +/- 20 Omega, n = 7). Acute vagotomy during ischaemia abruptly increased HR (from 155 +/- 11 to 193 +/- 15 beats min(-1)) and MEI (+12 +/- 1.1 Omega, from 663 +/- 18 Omega). In contrast, VNS during ischaemia (n = 11) abruptly reduced HR (from 206 +/- 6 to 73 +/- 9 beats min(-1)) and MEI (-16 +/- 2 Omega, from 700 +/- 44 Omega). These effects of VNS were eliminated by pacing but not by bilateral stellectomy. Vagal nerve stimulation during CAO also attenuated ECG-derived indices of ischaemia (e.g. ST segment, 0.22 +/- 0.03 versus 0.15 +/- 0.03 mV) and of rate-corrected repolarization dispersion [terminal portion of T wave (TPEc), 84.5 +/- 4.2 versus 65.8 +/- 5.9 ms; QTc, 340 +/- 8 versus 254 +/- 16 ms]. Vagal nerve stimulation during myocardial ischaemia exerts negative chronotropic effects, limiting early ischaemic electrotonic uncoupling and dispersion of repolarization, possibly via a decreased myocardial metabolic demand.

Changes in myocardial electrical impedance in human heart graft rejection

Monitoring of post-transplant heart rejection is currently based on endomyocardial biopsy analysis. This study aimed to assess the effects of heart graft rejection on myocardial electrical impedance. Twenty-nine cardiac transplant patients and 9 controls underwent measurement of myocardial electrical impedance using a specifically designed amplifying system. The module and phase angle of myocardial impedance were measured. Histopathological rejection grading was performed according to ISHLT classification. Fifty impedance tests were performed in transplanted patients. Myocardial impedance (Z) was higher in controls than in transplanted patients (p<0.001) and followed a progressive decline at increasing current frequencies (p<0.001). Likewise, the phase angle of impedance in controls ranged from positive values at low frequencies to negative values at higher frequencies (from 2.5+/-0.9 degrees at 10 kHz to -3.8+/-2.1 degrees at 300 kHz, p<0.001). Rejection was associated with a significant decrease in myocardial impedance (Z) (15+/-6.6 Omega in grade 0, 13+/-6.0 Omega in grade 1A, and 3.3+/-0.9 Omega in grade 3A at 10 kHz, p<0.003). Mild degrees of cardiac graft rejection are associated with significant changes in myocardial electrical impedance in transplant patients. Further clinical investigation is warranted to assess the potential of cardiac impedance to detect heart graft rejection.

Electrotonic remodeling following myocardial infarction in dogs susceptible and resistant to sudden cardiac death

Passive electrical remodeling following myocardial infarction (MI) is well established. These changes can alter electrotonic loading and trigger the remodeling of repolarization currents, a potential mechanism for ventricular fibrillation (VF). However, little is known about the role of passive electrical markers as tools to identify VF susceptibility post-MI. This study investigated electrotonic remodeling in the post-MI ventricle, as measured by myocardial electrical impedance (MEI), in animals prone to and resistant to VF. MI was induced in dogs by a two-stage left anterior descending (LAD) coronary artery ligation. Before infarction, MEI electrodes were placed in remote (left circumflex, LCX) and infarcted (LAD) myocardium. MEI was measured in awake animals 1, 2, 7, and 21 days post-MI. Subsequently, VF susceptibility was tested by a 2-min LCX occlusion during exercise; 12 animals developed VF (susceptible, S) and 12 did not (resistant, R). The healing infarct had lower MEI than the normal myocardium. This difference was stable by day 2 post-MI (287 +/- 32 Omega vs. 425 +/- 62 Omega, P < 0.05). Significant differences were observed between resistant and susceptible animals 7 days post-MI; susceptible dogs had a wider electrotonic gradient between remote and infarcted myocardium (R: 89 +/- 60 Omega vs. S: 180 +/- 37 Omega). This difference increased over time in susceptible animals (252 +/- 53 Omega at 21 days) due to post-MI impedance changes on the remote myocardium. These data suggest that early electrotonic changes post-MI could be used to assess later arrhythmia susceptibility. In addition, passive-electrical changes could be a mechanism driving active-electrical remodeling post-MI, thereby facilitating the induction of arrhythmias.

Electrotonic Remodeling Following Myocardial Infarction: A Link to Sudden Cardiac Death?

A potential mechanism for ventricular fibrillation (VF) and sudden cardiac death following myocardial infarction (MI) is the remodeling of repolarization currents, leading to increased action potential duration and dispersion of repolarization. Recently, it has been shown in vitro that electrotoni c loading, resulting from heterogene ities in the ventricle, triggers the remodelin g of the Ito current. Thus, we studied electrotonic coupling in the post-MI heart, as measured by myocardial electrical impedance (MEI). Infarcts were induced in dogs by LAD coronary artery ligation. The dogs were instrumented with MEI electrodes in normal (LCX and LAD) and infarcted myocardium. After recovery, MEI was measured in awake-unsedated animals 1, 2, and 7 days after MI. Subsequently, VF-susceptibility was tested by a 2-min LCX occlusion during submaximal exercise; 11 animals developed VF (susceptible, S) and 10 did not (resistant, R). Healing myocardial infarct had significantly lower MEI than normal myocardium (see figure). This difference was steady by day 2 post-MI (287±8.5 vs. 425±16.7 Ω, ANOVA P<0.05). Furthermore, significant differences were observed between resistant and susceptible animals: One week after MI, susceptible dogs had a wider electrotonic disparity between remote myocardium and scar (R: 86.5±20.7 vs. S: 183.7±12.6Ω, P<0.05). These data suggest that electrotonic remodeling following MI may contribute to malignant ventricular arrhythmias.

Vacuum-assisted apical suction devices induce passive electrical changes consistent with myocardial ischemia during off-pump coronary artery bypass graft surgery

Off-pump coronary artery bypass graft surgery is common therapy to completely revascularize diseased hearts. In order to graft posterior arteries in this procedure, the heart must be lifted from the chest cavity and manipulated to expose the surgical field using an apical suction device. This suction device may cause unwanted myocardial ischemia. In this observational study, we measured myocardial electrical impedance, a parameter that responds to myocardial ischemia, as well as ST-segment changes during off-pump coronary artery bypass graft surgery in 12 patients with two-vessel coronary artery disease undergoing revascularisation of the left anterior descending and the posterior descending coronary arteries. During the posterior descending artery revascularisation phase of the procedure the apical suction device was oriented over the electrodes used to measure myocardial electrical impedance, thus allowing us the opportunity to assess myocardial ischemia in this region of the heart. In these 12 patients, myocardial electrical impedance progressively increased under the suction device during posterior coronary artery revascularisation, suggesting that myocardial ischemia developed in this region of the myocardium. ST-segment changes were negligible while the heart was vertically displaced (and the suction device attached), but increased immediately when the heart was returned to the neutral anatomical position. Our data suggest that the apical suction device may cause ischemia while the heart is vertically displaced and electrically disconnected from the body. Under these conditions, ST-segment changes may not detect myocardial ischemia. Myocardial electrical impedance has the potential to reliably detect intraoperative myocardial ischemia under these circumstances.

Myocardial Electrical Impedance Response to Submaximal Exercise in Dogs with Healed Infarcts

Myocardial Electrical Impedance Response to Submaximal Exercise in Dogs with Healed Infarcts

Early time course of myocardial electrical impedance during acute coronary artery occlusion in pigs, dogs, and humans

Changes in myocardial electrical impedance (MEI) and physiological end points have been correlated during acute ischemia. However, the importance of MEI's early time course is not clear. This study evaluates such significance, by comparing the temporal behavior of MEI during acute total occlusion of the left anterior descending coronary artery in anesthetized humans, dogs, and pigs. Here, interspecies differences in three MEI parameters (baseline, time to plateau onset, and plateau value normalized by baseline) were evaluated using Kruskal-Wallis ANOVA and post hoc tests (P < 0.05). Noteworthy differences in the MEI time to plateau onset were observed: In dogs, MEI ischemic plateau was reached after 46.3 min (SD 12.9) min of occlusion, a significantly longer period compared with that of pigs and humans [4.7 (SD 1.2) and 4.1 min (SD 1.9), respectively]. However, no differences could be observed between both animal species regarding the normalized MEI ischemic plateau value (15.3% (SD 4.7) in pigs, vs. 19.6% (SD 2.6) in dogs). For all studied MEI parameters, only swine values resembled those of humans. The severity of myocardial supply ischemia, resulting from coronary artery occlusion, is known to be dependent on collateral flow. Thus, because dogs possess a well-developed collateral system (unlike humans or pigs), they have shown superior resistance to occlusion of a coronary artery. Here, the early MEI time course after left anterior descending coronary artery occlusion, represented by the time required to reach ischemic plateau, was proven to reflect such interspecies differences.

Myocardial Electrical Impedance Responds to Ischemia and Reperfusion in Humans

Myocardial electrical impedance (MEI) is correlated to ischemia and reperfusion of the heart muscle. The entire body of work with MEI to this point has been carried out in animal subjects in vivo and excised tissue samples. In this study, we measured MEI clinically for the first time in human patients who were undergoing off-pump coronary artery bypass (OPCAB) surgery. MEI was measured with a monitor designed in this laboratory and approved by the FDA for use on human subjects. Our patient population (n = 18) had a 70%-100% stenosis of the diseased coronary artery targeted for bypass. We measured MEI continuously during surgery and at 3, 6, 24, and 72 h postoperatively from two temporary pacing electrodes attached to the heart muscle. Absolute baseline impedance ranged from 173 to 729 ohms. MEI increased with occlusion of the diseased artery prior to bypass. The percent increase from baseline was inversely correlated to the percent stenosis of the diseased artery. MEI decreased below baseline immediately on reperfusion following bypass in all patients and continued decreasing over the measurement period. MEI is a reliable clinical indicator of ischemia and reperfusion in humans and may indicate the effectiveness of coronary artery surgery. The parameter may have monitoring and diagnostic value in heart disease in humans.

Effect of sarcolemmal rupture on myocardial electrical impedance during oxygen deprivation

Plasma membrane disruption is a characteristic feature of cell death induced by hypoxia or ischemia. Here, we investigated whether analysis of tissue electrical impedance allows detection of ongoing cell membrane rupture and necrotic cell death in hypoxic or ischemic myocardium. Twenty-eight isolated rat hearts were submitted to 5 h of ischemia (n = 8) or hypoxia (n = 20). Myocardial electrical impedance and lactate dehydrogenase (LDH) release were monitored. The time course of hypoxia-induced cell death was modified by altering pH (pH 7.4 or 6.4, 5 h) or by adding 3 or 10 mM glycine. Ischemia and hypoxia induced an increase in electrical impedance, followed by a plateau, and later a reduction. During hypoxia, LDH release started after a prolonged lapse of time (80.00 +/- 8.37 min at pH 7.4 and 122.50 +/- 11.82 min at pH 6.4). The onset of LDH release was followed by the onset of the late reduction in electrical impedance, and both were delayed by acidic pH (P < 0.05) and by glycine (P < 0.05). The times of onset of LDH release and of late electrical changes were significantly correlated (r = 0.752, P < 0.001). In separate experiments, induction of sarcolemmal rupture with Triton X-100 (n = 6) mimicked the late effects of ischemia or hypoxia on tissue impedance. The protective effects of glycine and acidosis on membrane disruption were confirmed (propidium iodide) in energy-deprived HL-1 cardiomyocytes. These results describe for the first time a late fall in electrical impedance in myocardium submitted to prolonged oxygen deprivation and demonstrate that this fall allows detection of ongoing cell necrosis.

Autologous skeletal myoblasts restore the myocardial electrical impedance, but not the refractory period of infarcted myocardium: engraftment versus integration?

Introduction: Autologous skeletal myoblasts (ASM) can survive within areas of myocardial infarct. However, little evidence exists as to whether these skeletal fibers develop and become integrated (electromechanically coupled) with the host myocardium. Myocardial electrical impedance (MEI) is sensitive to physiological changes in regional tissue metabolism, while the myocardial refractory period (RP) is sensitive to changes in integrated intercellular electrochemistry of the myocardium. Methods: Myocardial infarction was created in sheep (N = 7) by means of coronary microembolization. Myocardial impedance electrodes were placed in remote (CTRL) and infarcted areas. Animals were injected (in the infarct) with up to 5.0 × 10^8 ASM (INF+ASM; N = 4) or cell-media (INF; N = 3). MEI and RP were measured in awake, unsedated animals at 1, 7, 14 and 21 days following ASM/cell-media injection. Random night-time ECG (telemetry) monitoring was conducted to evaluate for the presence of premature ventricular contractions (PVCs) or other ectopy. Results: ASM-derived myofibers were found aligned and apposed to cardiac myocytes, however, no connexin 43 was identified in skeletal myocytes. At Day 1, the MEI and RP of infarcted myocardium (361±20Ω & 178±4ms) differed (P<0.05) from that of remote myocardium (480±25Ω & 205±8ms). After 21 days, the MEI difference remained unchanged in cell-media animals (470±71Ω vs. 584±27Ω) but decreased significantly with ASM, reaching control (remote) values (503±20Ω vs. 522±24Ω, see figure). However, no significant change in RP or PVC count (21 pvc/hr; range: 3–38) was observed after Day 1. Discussion: The normalization of passive electrical properties (MEI) of the infarcted myocardium after ASM injection may represent ASM development, engraftment, and the revitalization of myocardial scar by skeletal myofibers. However, the lack of changes in measured RP suggests that engrafted skeletal myofibers may not impact active electrochemical properties of the myocardium.

Pre-treatment with the Na+/H+ exchange inhibitor cariporide delays cell-to-cell electrical uncoupling during myocardial ischemia.

Inhibition of Na(+)-H(+) exchange (NHE) delays the onset of myocardial rigor contracture during ischemia. The aim of this study was to analyse the effects of NHE inhibition on cell-to-cell electrical uncoupling during myocardial ischemia/reperfusion. Twenty-six isolated rat hearts and 23 in situ porcine hearts were submitted to no-flow ischemia followed by reperfusion, with or without pre-treatment with cariporide (7 microM in rats and 3 mg/kg in pigs). Ischemic rigor and hypercontracture, conduction velocity and myocardial electrical impedance were monitored. Pre-treatment with cariporide delayed ATP depletion (luminescence assay in rat myocardium) and onset of rigor contracture (tension recordings or ultrasonic crystals) during ischemia both in rat and pig hearts (P<0.05). In addition, cariporide delayed the onset of sharp changes in tissue resistivity and phase angle in impedance recordings (four-electrode probes) from 10+/-1 to 13+/-1 min (P<0.001) in rat hearts, and from 22+/-1 to 38+/-2 min (P<0.001) in pigs. Blockade of impulse propagation (transmembrane action potentials in rat hearts) was also markedly delayed by cariporide (from 14+/-1 to 20+/-1 min, P<0.001). Reperfusion-induced LDH release in rat hearts and infarct size in pigs were markedly reduced by pre-treatment with cariporide. Inhibition of NHE with cariporide slows the progression of ischemic injury during myocardial ischemia, and delays the onset of cell-to-cell electrical uncoupling.