Effects of acidosis and NO on nicorandil-activated K(ATP) channels in guinea-pig ventricular myocytes.

1. Nicorandil is a hybrid compound of K(+) channel opener and nitrate. We investigated a possible interaction of acidosis and nitric oxide (NO)-donors on the nicorandil-activated ATP-sensitive K(+) channel (K(ATP)) in guinea-pig ventricular myocytes using the patch-clamp technique. 2. In whole-cell recordings, external application of 300 microM nicorandil activated K(ATP) in the presence of 2 mM intracellular ATP concentration ([ATP](i)) at external pH (pH(o)) 7. 4, but the activated current was decreased by reducing pH(o) to 6.5 - 6.0. 3. Single-channel recordings of inside-out patches revealed decreased open-state probability (P(o)) of K(ATP) activated by nicorandil with reducing internal pH (pH(i)) from 7.2 to 6.0, whilst the channel activity increased at low pH(i) in the absence of nicorandil. 4. Application of NO donors, 1 mM-sodium nitroprusside (SNP) or -NOR-3 to the membrane cytoplasmic side at pH(i) 7.2 increased the channel activity but decreased it at pH(i) 6.5 - 6.0. Neither removal of the drugs nor application of NO-scavengers reversed depression of channel activity induced by NO-donors. 5. We conclude that an increase in pH(o) and pH(i) depresses rather than stimulates the nicorandil-activated K(ATP). Since NO-donors at low pH(i) exhibited a similar trend, involvement of H(+) and NO interaction can be considered as a mechanism of decreased K(ATP) activated by nicorandil.

Usefulness of beta blocker therapy in patients with Takayasu arteritis and moderate or severe aortic regurgitation.

The objective of the present study was to evaluate the benefit of beta-blocker therapy for patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. Clinical and echocardiographic evaluation was performed in 20 Japanese women in a follow-up period of 7.0 +/- 2.0 years. The patients were divided into 2 groups: Group A (n=10) patients who did not receive beta-blockers, and Group B (n=10) patients treated with long-term (5.1 +/- 1.6 years) therapeutic doses of beta-blockers. Left ventricular wall thickness increased significantly in all Takayasu patients who did not receive beta-blockers. Consequently, a remarkable increment in left ventricular mass took place (232 +/- 59 to 361 +/- 79 g; p < 0.005). In the same group, progressive worsening of the symptoms, with no reduction in the percent fractional shortening, was observed in 2 patients, while reduction of this last index was present in 1 asymptomatic patient. On the other hand, among the patients who were treated with beta-blockers, left ventricular mass still increased in 6 cases, while it clearly decreased in the other 4 cases (290 +/- 171 to 284 +/- 61 g; NS). The increment in wall thickness or left ventricular mass observed among patients with beta-blocker therapy was clearly less than the one registered among those who had not received beta-blockers. Furthermore, no worsening of the symptoms and/or left ventricular performance was observed during the follow-up period for patients receiving beta-blockers. We conclude that beta-blocker therapy can slow and even reverse the progression of left ventricular hypertrophy in patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. The mechanism still needs to be elucidated. We believe an effective reduction in the excessive afterload imposed on the left ventricle to be most likely responsible, but cardiac beta-receptor up-regulation might also be involved. Deterioration of the clinical status and/or impairment of left ventricular function were not associated with beta-blocker therapy in our patients. Therefore, these agents can be used safely alone or in addition to standard anti-hypertensive therapy when attempting to reduce excessive afterload, in spite of the presence of severe aortic regurgitation.

Traumatic injuries of the face and hands.

Trauma to the face and hands initiates a comprehensive and often long-term course of treatment and reconstruction. Evaluation of the injuries and accurate on-going nursing assessment of the patient is essential to obtain optimal results. This article discusses both functional decision-making and aesthetic concerns.

Prospective, multicenter study of managing lower extremity venous ulcers.

Seventy patients with 90 venous ulcers were randomly assigned to hydrocolloid or conventional dressing and compression therapy at four study centers. The ulcers had been present for a mean of 47.8 in the control and 46.2 weeks in the treatment group and 42% of all patients had recurrent ulcers. Ulcers treated with hydrocolloid dressings reduced 71% and control treated wounds reduced 43% in area after 7.2 weeks of treatment. Thirty-four percent of all ulcers healed. Mean time to healing was 7 weeks for the hydrocolloid dressing group and 8 weeks for the control group. Most ulcers were less painful at final evaluation, but reduction in pain was more pronounced in hydrocolloid-dressed ulcers (p = 0.03). At baseline as well as during follow-up, significant differences between study centers were observed. Ulcers in patients in the United Kingdom were larger and less likely to heal (p = 0.001). Size of the ulcer at baseline was associated with treatment response and time to healing (p = 0.002). Percent reduction in ulcer area after 2 weeks was also correlated with treatment outcome (p = 0.004) and time to healing (p = 0.002). When all treatment outcome predictors were analyzed together, only percent reduction in area after 2 weeks remained statistically significant (p = 0.002), with percent reduction during the first 2 weeks of treatment > 30% predicting healing.

The healing wound: clinical management.

Although research is actively seeking and may even be finding ways to reduce the time required for wounds to heal, the current state of the art is still moderated by correct assessment, appropriate interventions, and most of all, prevention of inhibiting factors that delay the healing process.