After 52 weeks of treatment, RSG improved glycemic control but did not adversely affect LVEF in patients with T2DM and NYHA functional class I to II CHF. More fluid-related events occurred with RSG, although these generally did not lead to withdrawal from the study.

No abstract

Rosiglitazone added to background therapy with metformin provides greater reductions in microalbuminuria and blood pressure as compared with glyburide. These additional improvements in microalbuminuria, blood pressure and cardiovascular biomarkers were observed despite comparable improvements in glycemic control in both groups and may be related to the anti-inflammatory properties of rosiglitazone.

No abstract

Acetylcholine (ACh) decreased the contraction of rat ventricular cells within 20 s. ACh (3.1 x 10(-8) M) produced a half-maximal effect and 10(-6) M ACh produced a maximal effect (a 23.8 +/- 5.4% decrease; mean +/- SE, n = 11). During a 3-min exposure to ACh, the inotropic effect faded. Parallel changes were observed in action potential duration: ACh caused an immediate shortening of the action potential, but then the effect faded with time. The changes in action potential duration were the cause of the changes in contraction, because ACh had no effect on contraction when the contractions were triggered by voltage-clamp pulses of constant duration. The changes in action potential duration were the result of the activation of a K+ current (iK,ACh) by ACh. During an exposure to ACh, this current faded as a result of desensitization. iK,ACh was 6.3 times smaller in ventricular than in atrial cells. This may explain why the negative inotropic effect of ACh on atrial cells was greater: 1.0 x 10(-8) M ACh produced a half-maximal effect on atrial cells, and 10(-6) M ACh produced a near maximal effect (a 74.5 +/- 9.5% decrease; n = 4).

The mechanisms underlying electrical restitution (recovery of action potential duration after a preceding beat) were investigated in ferret ventricular cells. The time to 80% recovery (t80) of action potential duration was ∼204 ms. At a holding potential of −80 mV, the Ca2+ current (ICa) reactivated and the delayed rectifier K+ current (IK) deactivated very rapidly (t80: ∼32 and ∼93 ms, respectively). The kinetics of both currents are too fast to account for electrical restitution alone. The putative inward Na+−Ca2+ exchange current (INa‐Ca) produced by the Na+−Ca2+ exchanger in response to the intracellular Ca2+ transient reprimed (t80: 189 ms) with the same time course as mechanical restitution (recovery of contraction) and with a similar time course to electrical restitution. Substantial reduction of inward INa‐Ca, by buffering intracellular Ca2+ with the acetyl methyl ester form of BAPTA, shortened the action potential and greatly altered the electrical restitution curve. Subsequent addition of nifedipine (to block ICa) or 4–aminopyridine (4–AP) (to block the transient outward current, ITO) further altered the electrical restitution curve. Any time‐dependent current that contributes to the action potential is likely to affect the time course of electrical restitution. Although ICa:, IK and ITO were previously thought to be the only currents involved in electrical restitution, we conclude that inward INa‐Ca also plays an important role.

No abstract

CHF incidence may be greater when rosiglitazone is combined with sulfonylureas or insulin. When data were pooled, more events of myocardial ischemia were observed with rosiglitazone versus control. Final results from RECORD will allow a more rigorous evaluation of the cardiovascular safety profile.