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We used optical mapping to characterize the reentrant circuit of ventricular tachycardia (VT) during acute myocardial infarction (MI) in isolated canine left ventricular preparations.The nature of the reentrant circuit that underlies VT during acute MI is not well understood.Using optical mapping in isolated canine left ventricular preparations, we characterized the reentrant circuit of monomorphic VT (mean cycle length 245.3 +/- 15.6 ms, n = 7) induced by programmed stimulation during acute MI.Optical mapping during VT revealed a functional reentrant circuit consisting of four components: (1) a protected isthmus located between the infarction area and the functional line of block; (2) an entrance site located at one end of the isthmus; (3) an exit site located at the other end of the isthmus; and (4) an outer loop consisting of nonischemic normal tissue, connecting the exit and entrance sites. Rate-dependent slow conduction within the border zone was associated with significant changes (n = 6) in action potential amplitude (99.1 +/- 0.4 vs 71.4 +/- 0.6 mV, P.01), maximal diastolic potential (-80.6 +/- 0.2 vs -65.4 +/- 0.6 mV, P.05), action potential duration at 90% repolarization (APD(90); 188.4 +/- 1.0 vs 164.3 +/- 3.1 ms, P.05), and dV/dt (302.4 +/- 7.9 vs 168.5 +/- 3.6 V/s, P.05). Compared to preparations with no inducible VT (n = 7), formation of a functional line of block was the key mechanism for initiation of functional reentry in preparations with VT. When comparing preparations with sustained and nonsustained VT, preservation of slow conduction over the isthmus was the key component for maintenance of sustained VT.The reentrant circuit of monomorphic VT in the setting of acute MI involved both the infarction border zone and nonischemic normal tissue. The underlying mechanism is related to the presence of rate-dependent slow conduction and the development of a functional line of block in the border zone.

Thoracic Cord Stimulation and Cardiac Autonomics.Introduction: Thoracic spinal cord stimulation (SCS) has been used to treat angina pectoris and to produce cardiac autonomic control. We studied the effect of thoracic SCS on sinus node and AV nodal function to test the hypothesis that SCS modulated autonomic regulation of the electrophysiology of these structures. Methods and Results: The effects of thoracic SCS on sinus cycle length and AH interval were studied in 47 dogs in five experimental groups: group 1: intact autonomic nerves; group 2: bilateral ansae subclaviae transection and efferent stellate stimulation; group 3: ansae transection, bilateral vagi transection, and efferent stellate stimulation; group 4: bilateral vagi transection and efferent vagal stimulation; and group 5: bilateral vagal stimulation and bilateral ansae subclaviae transection. Under fluoroscopic guidance, the spinal stimulator electrode was advanced to the T1-T2 position and threshold determined by adjusting the output to produce muscle contraction. Parameters were measured at baseline prior to SCS and during SCS, at 90% threshold. Ansae subclaviae and vagi nerves were isolated using standard approaches. Stellate and vagal stimulation were each performed using a constant current stimulator and at three different frequencies. Sinus cycle length and AH intervals (the latter at constant right atrial pacing of 400 msec) were measured with and without SCS at baseline and at each level of nerve stimulation. Nitric oxide was measured using the coronary sinus overflow method, from a luminal balloon catheter placed deep in the coronary sinus. SCS resulted in an increase in sinus cycle length from 507 ± 23 msec to 544 ± 22 msec (P = 0.02) and AH interval from 71 ± 4 msec to 74 ± 4 msec (P = 0.03). Ansae subclaviae transection had no effect on this increase, while vagal transection eliminated the increase in sinus cycle length and AH with SCS. The increase in these parameters with SCS was maintained during both stellate stimulation (group 2) and vagal stimulation (group 5) across all three levels of neural stimulation. Conclusion: SCS appears to enhance parasympathetic activity, mediated via the vagus. This may have implications for use of thoracic SCS to treat chronic angina and perhaps prevent sudden cardiac death.

Recently, the routine use of dual-chamber implantable cardioverter defibrillators (DC-ICD) has been advocated over the single-chamber version (SC-ICD), but there are few reports of the frequency of complications between the 2 types of ICDs. Between July 1997 and April 1999, 178 consecutive patients underwent implantation of either a transvenous SC-ICDs (n=104) or a DC-ICDs (n=74). Twelve (16%) of the 74 patients with a DC-ICD had a total of 16 major complications compared with 6 (6%) of the 104 patients with a SC-ICD (p=0.01). The 16 DC-ICD complications included atrial lead dislodgment (4), ventricular lead malfunction (4), and pocket infection/hematoma (3), and the 6 SC-ICD complications included ventricular lead dislodgment (2) and pocket hematoma (3). Patients with a DC-ICD had less left ventricular function (29% vs 35%, p=0.035) and a higher prevalence of non-ischemic cardiomyopathies (48% vs 28%, p=0.0076). In conclusion, the DC-ICD may have a higher frequency of device- and lead-related major complications.

Objective: Recently, a novel missense mutation (R534C) in the S4 region of human ether-a-go-go-related gene ( HERG ) was identified in one Japanese LQT2 family. The S4 region presumably functions as a voltage sensor. However, it has not yet been addressed whether the S4 region of HERG indeed functions as a voltage sensor, and whether these residues play any role in abnormal channel function in cardiac repolarization. Methods: We characterized the electrophysiological properties of the R534C mutation using the heterologous expression system in Xenopus oocytes. Whole cell currents were recorded in oocytes injected with wild-type cRNA, R534C cRNA, or a combination of both. Results: Clinical features – QTc intervals of all affected patients with R534C mutation in HERG are prolonged ranging from 460 to 680 ms (averaged QTc interval>540 ms). One member of this family had experienced sudden cardiac arrest, and other suffered from recurrent palpitation. Electrophysiology – Oocytes injected with R534C cRNA did express functional channels with altered channel gating. Kinetic analyses revealed that the R534C mutation shifted the voltage-dependence of HERG channel activation to a negative direction, accelerated activation and deactivation time course, and reduced steady-state inactivation. Quantitative analyses revealed that this mutation did not cause apparent dominant-negative suppression. Computer simulation – Incorporating the kinetic alterations of R534C, however, did not reproduce prolonged action potential duration (APD). Conclusions: The data revealed that arginine at position 534 in the S4 region of HERG is indeed involved in voltage-dependence of channel activation as a voltage sensor. Our examination indicated that HERG current suppression in R534C mutation was the least severe among other mutations that have been electrophysiologicaly examined, while affected patients did show significant QT prolongation. This suggest that another unidentified factor(s) that prolong APD might be present.