Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers.

Anisotropy can lead to unidirectional conduction block that initiates reentry. We analyzed the mechanisms in patterned anisotropic neonatal rat ventricular myocyte monolayers. Voltage and intracellular Ca (Ca(i)) were optically mapped under the following conditions: extrastimulus (S1S2) testing and/or tetrodotoxin (TTX) to suppress Na current availability; heptanol to reduce gap junction conductance; and incremental rapid pacing. In anisotropic monolayers paced at 2 Hz, conduction velocity (CV) was faster longitudinally than transversely, with an anisotropy ratio [AR = CV(L)/CV(T), where CV(L) and CV(T) are CV in the longitudinal and transverse directions, respectively], averaging 2.1 ± 0.8. Interventions decreasing Na current availability, such as S1S2 pacing and TTX, slowed CV(L) and CV(T) proportionately, without changing the AR. Conduction block preferentially occurred longitudinal to fiber direction, commonly initiating reentry. Interventions that decreased gap junction conductance, such as heptanol, decreased CV(T) more than CV(L), increasing the AR and causing preferential transverse conduction block and reentry. Rapid pacing resembled the latter, increasing the AR and promoting transverse conduction block and reentry, which was prevented by the Ca(i) chelator 1,2-bis oaminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA). In contrast to isotropic and uniformly anisotropic monolayers, in which reentrant rotors drifted and self-terminated, bidirectional anisotropy (i.e., an abrupt change in fiber direction exceeding 45°) caused reentry to anchor near the zone of fiber direction change in 77% of monolayers. In anisotropic monolayers, unidirectional conduction block initiating reentry can occur longitudinal or transverse to fiber direction, depending on whether the experimental intervention reduces Na current availability or decreases gap junction conductance, agreeing with theoretical predictions.

Electrophysiological consequences of acute regional ischemia/reperfusion in neonatal rat ventricular myocyte monolayers.

BACKGROUND: Electrophysiological changes promoting arrhythmias during acute regional ischemia/reperfusion are challenging to study in intact cardiac tissue because of complex 3-dimensional myocardial and vascular geometry. We characterized electrophysiological alterations and arrhythmias during regional ischemia/reperfusion in a simpler 2-dimensional geometry of cultured neonatal rat ventricular myocyte monolayers. METHODS AND RESULTS: Optical mapping of intracellular Ca (Ca(i)) and voltage was performed with the use of Rhod 2-AM and Rh-237, respectively. Regional ischemia was mimicked by covering the central portion of monolayer with a glass coverslip, and reperfusion was mimicked by removing the coverslip. Monolayers were stained with fluorescent antibodies to detect total and dephosphorylated connexin-43 at various time points. During coverslip ischemia, action potential duration shortened, Ca(i) transient duration was prolonged, and local conduction velocity (CV) slowed progressively, with loss of excitability after 10.6 +/- 3.6 minutes. CV slowing was accompanied by connexin-43 dephosphorylation. During ischemia, spontaneous reentry occurred in 5 of 11 monolayers, initiated by extrasystoles arising from the border zone or unidirectional conduction block of paced beats. On reperfusion, excitability recovered within 1.0 +/- 0.8 minutes, but CV remained depressed for 9.0 +/- 3.0 minutes, promoting reentry in the reperfused zone. As connexin-43 phosphorylation recovered in the reperfused zone, CV normalized, and arrhythmias resolved. CONCLUSIONS: Acute regional ischemia/reperfusion in neonatal rat ventricular myocyte monolayers recapitulates electrophysiological alterations and arrhythmias similar to those observed during acute coronary occlusion/reperfusion in intact hearts. During early reperfusion, slow recovery from connexin-43 dephosphorylation leads to persistent CV slowing, creating a highly arrhythmogenic substrate.

Modulation of the sinus rate during ventricular fibrillation.

BACKGROUND: During supraventricular and ventricular tachycardia, the arterial baroreflex predominates with minimal contribution from the cardiopulmonary reflex. To our knowledge, the role of the arterial baroreflex gain (BRG) during and immediately following termination of ventricular fibrillation (VF) has not been characterized. OBJECTIVE: We hypothesized that (1) arterial BRG correlated with sinus node cycle length (SNCL) changes during VF, and that (2) the greater the arterial BRG, the greater the blood pressure (BP) recovery following successful defibrillation. METHODS: Arterial BRG was assessed in 18 patients referred for the implantation of a defibrillator incorporating an atrial lead. The average SNCL was measured during the 5 seconds prior to VF induction and the last 5 seconds during VF before defibrillation. Percent SNCL change (%DeltaSNCL) was determined. Arterial BP recovery was calculated as the difference in mean BP following defibrillation compared to during VF. RESULTS: Arterial BRG ranged between -3 and 18 ms/mmHg. During VF, SNCL shortened in 11 patients (group A, mean %DeltaSNCL =-15%), and surprisingly lengthened in seven patients (group B, mean %DeltaSNCL = 5%). There was no correlation between %DeltaSNCL and arterial BRG. In fact, arterial BRG in group A was lower when compared with group B (P = 0.075). Similarly, there was no correlation between arterial BRG and BP recovery. CONCLUSIONS: We found no correlation between arterial BRG and %DeltaSNCL during VF, or BP recovery following defibrillation. Our findings of SNCL lengthening in 7 of 18 patients suggest that in some patients, arterial BRG plays a minor role during VF with a greater contribution from the cardiopulmonary BRG.

Inappropriate ICD shocks for inappropriate reasons.

ICD shocks can result from a variety of etiologies; determining the proper etiology of the inappropriate shock is essential for correction of the problem. Electromagnetic interference (EMI) can mimic cardiac signals and cause inappropriate defibrillator shocks. We present two cases of inappropriate ICD shocks due to EMI and reversal of the proximal and distal DF-1 lead terminals of the ICD lead. These are two unusual etiologies for inappropriate defibrillator shocks.

Heart rate turbulence parameters correlate with post-premature ventricular contraction changes in muscle sympathetic activity.

BACKGROUND: Heart rate turbulence (HRT) has been shown to be vagally mediated with a strong correlation to baroreflex indices. However, the relationship between HRT and peripheral sympathetic nerve activity (SNA) after a premature ventricular contraction (PVC) remains unclear. OBJECTIVE: We sought to evaluate the relationship between HRT and the changes in peripheral SNA after PVCs. METHODS: We recorded postganglionic muscle SNA during electrocardiogram monitoring in eight patients with spontaneous PVCs. Fifty-two PVCs were observed and analyzed for turbulence onset (TO) and slope (TS). SNA was quantified during (1) the dominant burst after the PVC (dominant burst area) and (2) the 10 seconds after the dominant burst (postburst SNA). RESULTS: The mean TO was 0.1% +/- 4.6%, and the mean TS was 6.1 +/- 6.6. The dominant burst area negatively correlated with TO (r = -0.50, P = .0002). The postburst SNA showed a significant positive correlation with TO (r = 0.44, P = .001) and a negative correlation with TS (r = -0.42, P = .002). These correlations remained significant after controlling for either the PVC coupling interval or the left ventricular ejection fraction. CONCLUSIONS: Our findings highlight the relationship between perturbations in HRT and pathology in the sympathetic limb of the autonomic nervous system. Future studies are needed to evaluate the prognostic role of baroreflex control of sympathetic activity in patients with structural heart disease.

The effects of rate and irregularity on sympathetic nerve activity in human subjects.

BACKGROUND: We have recently shown that atrial fibrillation is associated with an increase in sympathetic nerve activity (SNA) compared with sinus rhythm. It remains unclear, however, whether these findings are true at various rates and whether the magnitude of sympathoexcitation is related to the degree of irregularity. OBJECTIVE: To determine the role of irregularity in mediating the SNA changes at various pacing rates. Univariate analysis showed that as the irregularity increased, SBP increased (r = 0.44, P < .001) but that MAP and DBP did not change significantly. METHODS: Using custom-made software, atrioventricular sequential pacing with predetermined rates (100, 120, and 140 bpm) and irregularities (standard deviation = 0%, 5%, 15%, and 25% of mean cycle length) was performed in 23 patients referred for electrophysiologic evaluation. Pacing at each rate/irregularity was performed for 2 minutes, with 2 minutes of recovery in between. Systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MAP), central venous pressure (CVP), and SNA were measured at baseline and during pacing. RESULTS: Univariate analysis showed that as the irregularity increased, SBP increased (r = 0.44, P < .001 but that MAP and DBP did not change significantly. A significant correlation was found between the pacing irregularity and SNA, with greater sympathoexcitation noted at greater degrees of irregularity (r = 0.2, P = .04). A five-variable linear model using DBP, MAP, CVP, and degree of pacing irregularity to predict SNA was highly statistically significant (r = 0.46, P < .001). After controlling for hemodynamic changes, for every 1% increase in irregularity, there was a 6.1% increase in SNA. CONCLUSION: We have shown that greater degrees of irregularity cause greater sympathoexcitation and that the effects of irregular pacing on SNA are independent of the hemodynamic changes.

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Case report: Radiofrequency catheter ablation of typical atrial flutter and the atrioventricular junction via the superior vena caval approach in a patient with a congenital absence of an inferior vena cava.

The absence of an inferior vena cava is a rare congenital condition often without clinical significance. Alternative venous approaches are often needed to treat these patients. We report a case of successful ablation of both isthmus dependent flutter and the AV junction using the superior vena cava in a patient with an inferior vena cava anomaly.

The use of the Doppler pulmonary artery velocity time integral to optimize placement of a ventricular pacing lead in a patient with Ebstein's anomaly.

Ebstein's anomaly is a rare congenital heart defect. Patients with severe symptomatic tricuspid regurgitation requiring surgical correction often have conduction system disease. We present a case of a 14 year-old girl with Ebstein's malformation and bioprosthetic tricuspid valve who required permanent pacing for symptomatic bradycardia. The placement of the right ventricular pacing lead was facilitated by the use of the Doppler pulmonary artery velocity time integral as a surrogate for stroke volume. This case demonstrates the importance of site-specific pacing and the utility of Doppler echocardiography to optimize lead placement and cardiac performance in patients with Ebstein's anomaly and advanced conduction system disease.

The importance of the evolution of ST-T wave changes for differentiating acute pericarditis from myocardial ischemia.

A 28-year-old, moderately obese man with dyslipidemia (low-density lipoprotein 163 mg/dL, high-density lipoprotein 33 mg/dL), hypertension, active tobacco use (1 pack per day), and a family history for premature coronary artery disease (CAD) initially presented with burning, nonexertional chest discomfort exacerbated by deep inspiration. His initial electrocardiogram (ECG; Fig. 1A) was interpreted as pericarditis because of the diffuse mild ST-segment elevation and PR-segment depression. An echocardiogram demonstrated normal left ventricular systolic function and a trivial pericardial effusion. He was treated with nonsteroidal antiinflammatories and his symptoms resolved. Follow-up ECG performed the next morning (Fig. 1B) demonstrated sinus rhythm, persistent mild ST elevation, and biphasic T waves in leads V3-V4 as well as in leads III and aVF. Four months later, the patient returned with similar symptoms of chest discomfort and was admitted with the diagnosis of unstable angina. The admission ECG was unremarkable showing no persistent PR or ST-T abnormalities. He was ruled out for myocardial infarction by serial enzymes. An exercise myocardial perfusion imaging study was obtained. The patient exercised for 7 minutes 33 seconds on a standard Bruce protocol, obtained 9.4 METs, and reached 69% of maximum predicted heart rate. His exercise ECG revealed up to 2.5 mm of ST-segment elevation in leads V3-V5 accompanied by chest discomfort. The patient's chest pain resolved with cessation of exercise and 1 sublingual nitroglycerin. The ECG returned to baseline within 3 minutes of recovery. He was referred for coronary angiography and was found to have a proximal left anterior descending (LAD) stenosis and underwent percutaneous coronary intervention with stenting. He was discharged home on postprocedure day 3.

AIDS associated with severe cor pulmonale and large pericardial effusion with cardiac tamponade.

Cardiac involvement in patients with advanced HIV/AIDS is common, including pericardial effusion and pulmonary hypertension. Although there is an increased incidence of pericardial effusion in patients with AIDS, most are small and asymptomatic. The presence of a pericardial effusion and/or pulmonary hypertension is associated with shortened survival. We present a case of a 43-year-old man with AIDS and advanced cardiovascular involvement who developed severe cor pulmonale and a large pericardial effusion with cardiac tamponade.