Recovery of advanced atrioventricular block by cilostazol.

We describe a case of advanced atrioventricular (AV) block, in which treatment with cilostazol was effective in recovering the AV conduction. The patient was referred to our hospital for close examination of the advanced AV block and permanent pacemaker implantation. Although the patient had experienced third-degree AV block with occasional AV synchrony for more than two days, the AV conduction completely recovered after treatment with oral cilostazol at 200 mg/day. Here we discuss the possible mechanism of the improvement in the AV conduction by cilostazol.

Roles of calcineurin and calcium/calmodulin-dependent protein kinase II in pressure overload-induced cardiac hypertrophy.

Calcineurin and calcium/calmodulin-dependent protein kinase (CaMK) II have been suggested to be the signaling molecules in cardiac hypertrophy. It was not known, however, whether these mechanisms are involved in cardiac hypertrophy induced by pressure overload without the influences of blood-derived humoral factors, such as angiotensin II. To elucidate the roles of calcineurin and CaMK II in this situation, we examined the effects of calcineurin and CaMK II inhibitors on pressure overload-induced expression of c-fos, an immediate-early gene, and protein synthesis using heart perfusion model. The hearts isolated from Sprague-Dawley rats were perfused according to the Langendorff technique, and then subjected to the acute pressure overload by raising the perfusion pressure. The activation of calcineurin was evaluated by its complex formation with calmodulin and by its R-II phosphopeptide dephosphorylation. CaMK II activation was evaluated by its autophosphorylation. Expression of c-fos mRNA and rates of protein synthesis were measured by northern blot analysis and by 14C-phenylalanine incorporation, respectively. Acute pressure overload significantly increased calcineurin activity, CaMK II activity, c-fos expression and protein synthesis. Cyclosporin A and FK506, the calcineurin inhibitors, significantly inhibited the increases in both c-fos expression and protein synthesis. KN62, a CaMK II inhibitor, also significantly prevented the increase in protein synthesis, whereas it failed to affect the expression of c-fos. These results suggest that both calcineurin and CaMK II pathways are critical in the pressure overload-induced acceleration of protein synthesis, and that transcription of c-fos gene is regulated by calcineurin pathway but not by CaMK II pathway.

Microvascular angina accompanied by epicardial coronary artery spasm.

A case of microvascular angina accompanied by coronary artery spasm is described. A 54-year-old woman had anginal pain at rest and during exercise. Both exercise testing and rapid atrial pacing caused significant ST depression in the inferior and all precordial leads. Exercise thallium myocardial scintigraphy was negative despite similar ST depressions. Coronary angiography revealed insignificant stenoses of the left anterior descending coronary artery after the injection of nitrate. Intracoronary acetylcholine provoked diffuse spasm of the artery with concurrent myocardial lactate production. Coronary flow reserve assessed with papaverine was 2.75. The combined use of amlodipine and high-dose nicorandil was effective for the treatment of angina.