Satoshi Takebayashi

Actions of Mibefradil, Efonidipine and Nifedipine Block of Recombinant T- and L-Type Ca2+ Channels with Distinct Inhibitory Mechanisms

We compared detailed efficacy of efonidipine and nifedipine, dihydropyridine analogues, and mibefradil using recombinant T- and L-type Ca²⁺ channels expressed separately in mammalian cells. All these Ca²⁺ channel antagonists blocked T-type Ca²⁺ channel currents (I_Ca(T)) with distinct blocking manners: I_Ca(T) was blocked mainly by a tonic manner by nifedipine, by a use-dependent manner by mibefradil, and by a combination of both manners by efonidipine. IC₅₀s of these Ca²⁺ channel antagonists to I_Ca(T) and L-type Ca²⁺ channel current (I_Ca(L)) were 1.2 µmol/l and 0.14 nmol/l for nifedipine; 0.87 and 1.4 µmol/l for mibefradil, and 0.35 µmol/l and 1.8 nmol/l for efonidipine, respectively. Efonidipine, a dihydropyridine analogue, showed high affinity to T-type Ca²⁺ channel.

Lysophosphatidylcholine augments Ca(v)3.2 but not Ca(v)3.1 T-type Ca(2+) channel current expressed in HEK-293 cells.

Lysophosphatidylcholine (LPC) has been shown to induce electrophysiological disturbances to arrhythmogenesis. However, the effects of LPC on the low-voltage-activated T-type Ca2+ channels in the heart are not understood yet. We found that LPC increases the T-type Ca2+ channel current (ICa.T) in neonatal rat cardiomyocytes. To further investigate the underlying modulatory mechanism of LPC on T-type Ca2+ channels, we utilized HEK-293 cells stably expressing α1G and α1H subunits (HEK-293/α1G and HEK-293/α1H), by use of patch-clamp techniques. A low concentration of LPC (10 µmol/l) significantly increased Cav3.2 ICa.T (α1H) that were similar to those observed in neonatal rat cardiomyocytes. Activation and steady-state inactivation curves were shifted in the hyperpolarized direction by 5.1 ± 0.2 and 4.6 ± 0.4 mV, respectively, by application of 10 µmol/l LPC. The pretreatment of cells with a protein kinase C inhibitor (chelerythrine) attenuated the effects of LPC on ICa.T (α1H). However, the application of LPC failed to modify Cav3.1 (α1G) ICa.T at concentrations of 10–50 µmol/l. In conclusion, these data demonstrate that extracellularly applied LPC augments Cav3.2 ICa.T (α1H) but not Cav3.1 ICa.T (α1G) in a heterologous expression system, possibly by modulating protein kinase C signaling.

Perioperative management for iatrogenic aortocoronary dissection during percutaneous coronary intervention

Aortocoronary dissection is a rare but serious complication. We report the case of a 72-year-old female with angina. Percutaneous coronary intervention was performed for right coronary artery disease. Manipulation of the guiding catheter led to aortocoronary dissection. A drug-eluting stent was immediately implanted in the right coronary ostium to seal the entry of the dissection. Computed tomography (CT) showed ascending aortic dissection. The patient was observed without surgery. CT performed the following day and showed the contrast in the false lumen which had disappeared. Clinicians are more likely to avoid surgical treatment if stenting successfully seals the entry of the coronary dissection.

Unique Technique for Open Surgical Repair after Failed Endovascular Aneurysm Repair with Proximal Anastomoses.

Endovascular aortic aneurysm repair (EVAR) has revolutionized the management of abdominal aortic aneurysms (AAAs), with lower perioperative morbidity and mortality compared to conventional surgical repair. However, late secondary re-interventions after EVAR are still needed before aneurysm rupture in many cases. A patient with impending rupture of an AAA associated with a type I endoleak 7 years after EVAR who was successfully treated with a unique technique of fixation of the proximal aortic neck taking into account the structure of the stent graft is reported. This technique offers a safe solution to late open conversion after failed EVAR.