Increasing access to nonprescription medicines: a global public health challenge and opportunity.

As escalating health-care costs continue to be a focus of public discourse, the populace has become increasingly attentive to its own health and lifestyle choices. Nonprescription (over-the-counter, OTC) medicines represent an important option in this evolving environment and, through novel "Rx-to-OTC" switch efforts, could expand beyond their traditional role in symptomatic relief of common conditions such as minor pain, coughs, colds, heartburn, and allergy. This is certainly not a new concept. In fact, the self-care movement has roots reaching into the past century. Pharmaceutical companies and their consumer-product subsidiaries or partners have long considered and, when feasible, invested in difficult OTC switch development programs.

Comparison of slow response action potentials from normal and hypertrophied myocardium.

Previous studies have shown that papillary muscles from hypertrophied cat right ventricles (RVH) exhibit altered mechanical properties which may be associated with defects in the excitation-contraction coupling process. Since calcium influx [as slow inward current (Isi) during the cardiac action potential is thought to be a major determinant of contractile state, we compared Isi-mediated slow response action potentials ( SRAPs ) in papillary muscles from cats with RVH, induced by chronic pulmonary artery constriction, to SRAPs from sham-operated controls. The results show that 1) when depolarized by elevated extracellular potassium (K+o, 22 mM), RVH muscles became inexcitable (as defined here) significantly faster than control muscles; 2) inexcitable RVH muscles required significantly more isoproterenol than controls to restore slow response activity; 3) at all isoproterenol concentrations tested, SRAPs from RVH muscles were reduced in amplitude and duration compared with controls; 4) SRAPs evoked by long duration stimulus pulses in the absence of isoproterenol were also markedly reduced in RVH; and 5) the relationship between resting potential and K+o was the same in both groups. If the alterations in SRAPs observed in RVH are produced by a smaller Isi, this change may be associated with the diminished inotropic state of cardiac muscle caused to hypertrophy due to pressure overload.

Isolation and morphology of calcium-tolerant feline ventricular myocytes.

A technique has been developed for isolating a high yield of Ca2+-tolerant rod-shaped myocytes from the right and left ventricles of cat myocardial tissue. Myocytes were prepared by retrograde perfusion of the coronary arteries via the aorta with a nominally Ca2+-free (20-30 microM) modified Krebs-Henseleit buffer containing 0.12% collagenase. After exposure to physiological levels of Ca2+ (1-2.5 mM), the cells retained rod-shaped morphology, exhibited clear cross striations, and excluded the dye trypan blue (0.4%). Initial percents of viable Ca2+-tolerant rod-shaped cells were 58.6 +/- 3.4 (SE) and 51.8 +/- 3.5 for right and left ventricular cells, respectively. Viability studies demonstrated that these values decreased approximately 10% at the conclusion of a 2-h incubation in 1 mM Ca2+. The total numbers of rod-shaped myocytes obtained were 4.48 X 10(7) and 3.89 X 10(7) in nominal (8-10 microM) and 1 mM Ca2+-containing buffer, respectively. A total of 3.44 +/- 0.40 X 10(6) rod-shaped Ca2+-tolerant myocytes was initially isolated per gram of tissue wet weight. Measurements of cell length, width, and sarcomere length demonstrated no significant differences between right and left ventricular cells suspended in nominal (8-10 microM) and 1 mM Ca2+-containing buffer. No significant difference was found in the percent of binucleate cells when right and left ventricular myocytes were compared. These results demonstrate that a stable population of Ca2+-tolerant myocytes with similar morphological characteristics can be isolated from the right and left ventricles of cat myocardium.

Cardiovascular effects of indapamide on frog hearts and open-chest cats.

Unlike related diuretics indapamide has been found by some investigators to be associated with a mild reduction in heart rate during its use as an antihypertensive agent. This investigation concerns the attempt to duplicate this phenomenon in animals and to elucidate possible mechanisms. In isolated frog hearts, high concentrations (0.3 mM) of indapamide decreased contractions 21.7 +/- 1.2% and rate 9.1 +/- 1.0%. This effect was not observed with chlorothiazide, acetazolamide, or furosemide and was not altered by atropine. Also in the frog heart, 0.03 mM indapamide reduced the stimulatory effects of isoproterenol and calcium ion and enhanced the inhibitory action of acetylcholine. In open-chest cats, after 30 min, indapamide (3 mg/kg, i.v.) elicited minor decreases in heart rate, aortic flow, and mean carotid pressure. When arterial pressure was rapidly reduced by acetylcholine (5 microgram/kg, i.v.) the resultant rise in aortic flow was significantly diminished by indapamide pre-treatment. Antifibrillatory activity was measured in the open-chest cat by determining the minimum electrical current, delivered to the right atrium, required to induce atrial fibrillation. Quinidine (5 mg/kg, i.v.) and chlorothiazide (10 mg/kg, i.v.) raised the fibrillatory threshold 94.3 +/- 10.1 % and 45.1 +/- 4.0 % respectively while indapamide displayed minimal activity.