Inducibility of Ventricular Arrhythmia 1 Year Following Treatment with Heavy Ion Irradiation in Dogs with Myocardial Infarction

Background: Targeted external heavy ion irradiation (THIR) of rabbit hearts 2 weeks after myocardial infarction (MI) reduced the vulnerability of fatal ventricular tachyarrhythmias (VT/VF) in association with the increased connexin43 (Cx43). Increased Cx43 was maintained for at least 1 year in normal rabbits, but the long-term antiarrhythmic effects in the MI model are unknown. We investigated the propensity for late potentials and VT/VF inducibility.Methods: Intracoronary injection of microspheres was performed to induce nontransmural MI in anesthetized eight beagles. Four beagles were treated with THIR (12C6+, 15 Gy) 2 weeks later (MI + THIR group), and four without THIR served as controls (MI group). Signal-averaged electrocardiography, programmed electrical stimulation, immunohistochemical analysis, and echocardiograms were performed at 1 year.Results: Filtered QRS duration was exacerbated after MI and remained unchanged for 1 year in the MI group (118 ± 1.4 ms), but significantly returned toward baseline in the MI + THIR group (109 ± 6.9 ms). Similarly, root mean square voltage of the last 40 ms was exacerbated after MI, but recovered after THIR. VT/VF inducibility decreased to 25% in the MI + THIR group compared with 100% in the MI group. Immunostaining Cx43 expression in cardiac tissues significantly increased by 24–45% in the MI + THIR group. Left ventricular ejection fractions remained within the normal range in both groups.Conclusion: A single exposure of the dog heart to 12C irradiation attenuated vulnerability to ventricular arrhythmia after the induction of MI for at least 1 year through the modulation of Cx43 expression

Changes in arrhythmogenic properties and five-year prognosis after carbon-ion radiotherapy in patients with mediastinum cancer

Introduction: Carbon-ion irradiation of rabbit hearts has improved left ventricular conduction abnormalities through upregulation of gap junctions. However, to date, there has been no investigation on the effect of carbon-ion irradiation on electrophysiological properties in human. We investigated this effect in patients with mediastinum extra-cardiac cancer treated with carbon-ion radiotherapy that included irradiating the heart. Methods and Results: In April–December 2009, eight patients were prospectively enrolled (including two male, aged 68.4 ± 17.2 years). They were treated with 44–72 Gray equivalent (GyE), with their hearts exposed to 1.3–19.1 GyE. High-resolution ambulatory electrocardiography was performed before and after radiotherapy to investigate arrhythmic events, late potentials (LPs), and heart rate variability. Five patients had pre-existing premature ventricular contraction (PVC)/atrial contraction (PAC) or paroxysmal atrial fibrillation (PAF)/AF; after irradiation, this improved in four patients with PVC/PAF/AF and did not deteriorate in one patient with PAC. Ventricular LP findings did not deteriorate and improved in one patient. In eight cases with available atrial LP findings, there was no deterioration, and two patients showed improvements. The low frequency/high frequency ratio of heart rate variability improved or did not deteriorate in the six patients who received radiation exposure to the bilateral stellate ganglions. During the five-year follow-up for the prognosis, six of the eight patients died because of cancer; there was no history of hospitalization for cardiac events. Conclusion: Although this preliminary study has several limitations, carbon-ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction

Ordinary Autonomic Unbalance Can Reflect Diagnosis of Neurally Mediated Reflex Syncope

Background: In the present study we investigated autonomic dysfunction using hemodynamics and analysis of heart rate variability (HRV) following ambulatory blood pressure monitoring (APBM) in patients with neurally mediated reflex syncope (NMRS). In addition, we evaluated the usefulness of ABPM for diagnosing NMRS. Methods: In all, 88 consecutive patients with syncope and 12 controls (Group C) were subjected to a head-up tilt (HUT) test (80°, 30 min). If no syncope or presyncope occurred, the HUT test was repeated in the patient group following drug loading (ATP, isoproterenol, and/or isosorbide dinitrate). Results: Forty patients had a positive HUT test, with or without drug loading (Group P) ; the HUT test was negative in 48 patients, even after drug loading. Average daytime systolic and diastolic blood pressure (SBP and DBP, respectively) was significantly lower in Group P than in Group C (P = 0.042 and P = 0.047, respectively). The average standard deviation of SBP at night (SD-SBPNight) was significantly higher in Group P than in Group C (P = 0.004). HRV analysis revealed a significantly higher daytime high-frequency component in Group P than in Group C (P = 0.041). Conclusion: The results of the present study suggest that lower daytime blood pressure and a larger SD-SBPNight, as determined by ABPM, are associated with vagal nerve hyperactivity and sympathetic hypoactivity in patients with NMRS. Thus, an inadequate circadian rhythm in blood pressure variation, as identified by ABPM, may be useful for the diagnosis of NMRS