Enhancing effects of salicylate on tonic and phasic block of Na+ channels by class 1 antiarrhythmic agents in the ventricular myocytes and the guinea pig papillary muscle

AbstractObjective: To study the interaction between salicylate and class 1 antiarrhythmic agents. Methods: The effects of salicylate on class 1 antiarrhythmic agent-induced tonic and phasic block of the Na+ current (INa) of ventricular myocytes and the upstroke velocity of the action potential (Vmax) of papillary muscles were examined by both the patch clamp technique and conventional microelectrode techniques. Results: Salicylate enhanced quinidine-induced tonic and phasic block of INa at a holding potential of −100 mV but not at a holding potential of −140 mV; this enhancement was accompanied by a shift of the h∞ curve in the presence of quinidine in a further hyperpolarized direction, although salicylate alone did not affect INa. Salicylate enhanced the tonic and phasic block of Vmax induced by quinidine, aprindine and disopyramide but had little effect on that induced by procainamide or mexiletine; the enhancing effects were related to the liposolubility of the drugs. Conclusions: Salicylate enhanced tonic and phasic block of Na+ channels induced by class 1 highly liposoluble antiarrhythmic agents. Based on the modulated receptor hypothesis, it is probable that this enhancement was mediated by an increase in the affinity of Na+ channel blockers with high lipid solubility to the inactivated state channels

Prevalence and complications of hypouricemia in a general population: A large-scale cross-sectional study in Japan

<div><p>Backgrounds</p><p>Hypouricemia was reported as a risk factor for exercise-induced acute renal injury (EIAKI) and urinary stones. However, the prevalence of kidney diseases among hypouricemic subjects has not been evaluated. This study was conducted to clarify the prevalence of hypouricemia and the association of hypouricemia with kidney diseases by using a large-scale Japanese population data.</p><p>Methods</p><p>This study is a retrospective cross-sectional study at the Center for Preventive Medicine, St. Luke’s International Hospital, Tokyo, Japan, and Sanin Rousai Hospital, Yonago, Japan. We analyzed the medical records of 90,143 Japanese subjects at the center in St. Luke’s International Hospital, Tokyo, and 4,837 subjects in Sanin Rousai Hospital, Yonago, who underwent annual regular health check-up between January 2004 and June 2010. We defined hypouricemia as serum uric acid level of ≤2.0 mg/dL. We checked the medical history of all the study subjects and compared the rates of complications including urinary stones and kidney diseases among those with or without hypouricemia.</p><p>Results</p><p>The prevalence of hypouricemia was 0.19% in St. Luke’s International Hospital, Tokyo, and 0.58% in Sanin Rousai Hospital, Yonago. The prevalence of hypouricemia in women was larger than that in men both in Tokyo (0.31% vs 0.068%, p<0.001) and in Yonago (1.237% vs 0.318%, p<0.001). Among 172 hypouricemic subjects (30 men), the rates of previous urinary stones and kidney diseases (including nephritis/nephrosis) were 1.2% (3.3% men, 0.7% women) and 2.3% (10% men, 0.7% women), respectively. Hypouricemic men had a 9-fold higher rate of previously having kidney diseases compared to non-hypouricemic men (p<0.001). However, the rates of other diseases including urinary stones were not significantly different between the two groups.</p><p>Conclusions</p><p>Hypouricemia was associated with a history of kidney disease especially in men.</p></div

Characteristics of the study subjects.

<p>Characteristics of the study subjects.</p

The differences of medical history between hypouricemia and non-hypouricemia.

<p>The differences of medical history between hypouricemia and non-hypouricemia.</p

The distribution of hypouricemia among each age by sex.

<p>In women, the number of hypouricemia subjects was decreased with age.</p

The distribution of hypouricemia among serum uric acid level by sex.

<p>The number of the women subjects whose serum uric acid of 2.0 mg/dL was 47. The number of the total (men and women) subjects whose serum uric acid of 2.0 mg/dL was 49. These numbers were above this graph limit (25 subjects), and we showed the numbers in the graph.</p