Kazunori Moritani

Blockade of ATP-sensitive potassium channels by 5-hydroxydecanoate suppresses monophasic action potential shortening during regional myocardial ischemia

SummaryWe tested 5-hydroxydecanoate (5-HD), a specific blocker of ATP-sensitive potassium channels (IK.ATP), to determine if it mitigates electrophysiologic changes produced by regional myocardial ischemiain vivo. A sequence of 5-minute occlusion of the distal LAD and 30-minute reperfusion was repeated while recording the monophasic action potential (MAP) and bipolar electrogram (EG) from the epicardial center of the ischemic myocardium in anesthetized dogs. 5-HD (30 mg/kg, IV) or glibenclamide (0.15 or 0.3 mg/kg, IV) was administered before the third occlusion, and the data were compared to the second occlusion data. 5-HD did not affect baseline MAP duration at 90% and 50% repolarization (APD90, APD50) before LAD occlusion but suppressed occlusion-induced shortening of APD90 (16 ± 2% during the second occlusion vs. 5 ± 3% during the third occlusion, n=8, p<0.01) and APD50 (16 ± 3% vs. 10 ± 3%, n=8, p<0.05). Pretreatment with glibenclamide also suppressed occlusion-induced MAP shortening and eliminated an additional effect of 5-HD (n = 3). 5-HD did not affect the occlusion-induced increase in duration and activation time of EG. 5-HD, as well as glibenclamide, suppressed regional ischemia-induced MAP shortening, probably by blocking activation of IK.ATP, without affecting conduction delay. These differential effects of 5-HD on repolarization and conduction during the early phase of regional ischemia might have the potential to suppress reentrant ventricular arrhythmias.

Nicorandil augments regional ischemia-induced monophasic action potential shortening and potassium accumulation without serious proarrhythmia

Nicorandil is a clinically used nitrovasodilator that has a property as an opener of ATP-sensitive potassium (KATP) channels in vitro. We examined whether nicorandil at a clinically used dose augmented regional ischemia-induced monophasic action potential (MAP) shortening and increase in extracellular potassium concentration ([K+]o), and how it affected arrhythmia occurrence. Five-minute occlusion of a distal site of the left anterior descending coronary artery (LAD) was repeated at 30-min intervals in anesthetized open-chest dogs while recording MAP or measuring [K+]o with a potassium-sensitive valinomycin electrode from the epicardial center of the ischemic myocardium. Nicorandil (0.2-0.5 mg/kg) was administered intravenously (i.v.) 5 min before the third occlusion, and the data were compared with those during the second occlusion (control). During the second occlusion, MAP duration at 90% repolarization (APD90) shortened (mean rate for 5 min, 13 +/- 3%, n = 11) and [K+]o increased from 3.7 +/- 0.1 to 6.2 +/- 0.8 mM at 5 min (n = 12). These changes were reversed < or = 3 min after reperfusion. Before the third occlusion, baseline APD90 and [K+]o were not altered by nicorandil; however, the extent of occlusion-induced shortening of APD90 (25 +/- 4%) and [K+]o increase (7.8 +/- 1.6 mM) was augmented by the pretreatment. The drug effect was attenuated by a concomitant pretreatment with 5-hydroxydecanoate, a specific blocker of KATP channels (n = 2). The prevalence of ventricular fibrillation (VF) during occlusion/reperfusion sequence was reduced after nicorandil (1 of 25 vs. 5 of 25) without de novo VF. These results suggest that nicorandil at a clinical dose facilitates regional ischemia-induced activation of myocardial KATP channels without causing serious proarrhythmia. Such a property might help protect the myocardium against ischemia/reperfusion damage.

Ischemic Postconditioning with Lactate-Enriched Blood in Patients with Acute Myocardial Infarction

postconditioning protocol was modified as follows. The duration of each brief reperfusion was gradually increased from 10 to 60 s in a stepwise manner. This approach sought to prevent the rapid and abrupt washout of lactate during the very early phase of reperfusion. Each brief ischemic period lasted 60 s. At the end of each brief reperfusion, lactate was supplied by injecting lactated Ringer’s solution, containing 28 m M lactate (Lactec Injection, Otsuka Pharmaceutical Company, Tokyo, Japan), directly into the culprit coronary artery (20 ml for the right coronary artery and 30 ml for the left coronary artery) immediately before balloon inflation. This approach allowed trapping of lactate inside the ischemic myocardium during each brief repetitive ischemic period. After 7 cycles of balloon inflation and deflation (the brief reperfusion of 60 s was repeated twice at the end of the postconditioning protocol), full reperfusion was performed. Stenting was then performed and percutaneous coronary intervention (PCI) was completed. Thrombosuction was implemented only after the completion of postconditioning procedures, if needed. Blood samples were obtained for the measurement of serum creatine kinase (CK) and creatine kinase MB (CK-MB) every 4 h until the values peaked. Rest thallium-201 imaging was performed on all paLimalanathan et al. [1] and Tarantini et al. [2] reported study designs for examining the protective effects of postconditioning in patients with acute myocardial infarction (MI) in volume 116 of Cardiology in 2010. However, recent clinical trials have not elucidated the protective effects of postconditioning [3, 4] . We therefore propose here a new postconditioning protocol. The protective effect of postconditioning is thought to result from delayed recovery from intracellular acidosis during the reperfusion period [5] . Assuming this is the case, prolonging the delay in intracellular acidic recovery may increase this protective effect. It is generally accepted that lactate accumulation is responsible for intracellular acidosis during ischemia. As a higher extracellular lactate concentration impedes lactate transport from inside the cells [6] , reperfusion with lactate-enriched blood should protect myocardial cells against reperfusion injury through prolonged intracellular acidification. We therefore modified the original postconditioning protocol by using lactated Ringer’s solution to achieve controlled reperfusion with tissue oxygenation and minimal lactate washout from the cells. A series of 6 consecutive patients in various stages of acute MI were treated using our modified postconditioning protocol at Tachikawa Hospital ( table 1 ). The original Received: January 17, 2013 Accepted after revision: February 7, 2013 Published online: May 24, 2013

Differential Role of Epicardial and Endocardial KATP Channels in Potassium Accumulation During Regional Ischemia Induced by Embolization of a Coronary Artery with Latex

Epicardial and and Endocardial [K+]0 Rise and KATP Channels. Introduction: KATP channels are activated predominantly in the epicardium during regional ischemia. Therefore, the role of KATP channels in ischemia‐induced rise of extracellular potassium concentration ([K+]o) might he greater in the epicardium.

A case of echocardiographic evaluation of ruptured pseudoaneurysm of the mitral-aortic intervalvular fibrosa by infective endocarditis.

This report describes an unusual case of ruptured pseudoaneurysm (PSA) of mitral-aortic intervalvular fibrosa (MAIVF) caused by infective endocarditis. The PSA ruptured into the left sinus of Valsalva in addition to the left atrium, resulting in complicated shunting among the aorta, left ventricle and left atrium, leading to refractory heart failure. The transesophageal echocardiography provided the precise information concerning the anatomical detail of the PSA, which is crucial for the surgical repair. This is the first report describing a patient with PSA of MAIVF with two rupture sites.

Impact of postconditioning with lactate-enriched blood on in-hospital outcomes of patients with ST-segment elevation myocardial infarction

BACKGROUND Reperfusion injury offsets the beneficial effects of reperfusion therapy for ST-segment elevation myocardial infarction (STEMI). In our previous reports, postconditioning with lactate-enriched blood (PCLeB) induced excellent microcirculation recovery and less inflammation in STEMI patients. This study aimed to determine the in-hospital outcomes of STEMI patients treated using PCLeB. METHODS Fifty-five consecutive STEMI patients were treated using PCLeB (Age 66.6±13.8years, 76.4% men) within 12h of symptom onset. In our modified postconditioning protocol, the duration of each brief reperfusion was prolonged from 10s to 60s in a stepwise manner. Lactated Ringers solution (20-30mL) was injected directly into the culprit coronary artery at the end of each brief reperfusion and the balloon was quickly inflated at the lesion site, whereby lactate could be trapped inside the ischemic myocardium. Each brief ischemic period lasted 60s. After 7cycles of balloon inflation and deflation, full reperfusion was performed. Thereafter, stenting was performed and percutaneous coronary intervention (PCI) was completed. RESULTS The mean corrected thrombolysis in myocardial infarction frame count was 20.1±10.1 after PCI completion. The mean peak serum creatine kinase and creatine kinase-MB levels were 2751±2227IU/L and 276±181IU/L respectively. None of the study patients died during their hospital stay or required continuation of oral diuretic or inotropic therapy for heart failure on discharge. CONCLUSIONS PCLeB led to zero in-hospital mortality and no overt heart failure on discharge in 55 consecutive STEMI patients undergoing reperfusion therapy.

Shifting Calcium Plaque in Progressive Aortic Dissection

An 80-year-old man with a 1-day history of chest pain was referred to our cardiology clinic. The patient’s right arm blood pressure, pulse, and temperature were found to be 81/53 mm Hg, 71 beats/min, and 37.4°C, respectively. Electrocardiography was unremarkable. Chest radiography revealed a widened mediastinum and a small amount of pleural effusion at …