Dobutamine-induced spontaneous rhythmic contractions of human isolated atrial strips mimic physiological responses of intact human heart.

We have shown that in isolated human atrial strips the ß1-adrenoceptor agonist dobutamine can induce spontaneous, stable and durable rhythmic contractions. The amplitude and frequency of these contractions were regulated endogenously by the tissue. We tested whether the spontaneously contracted atrial strips could be used as an experimental assay model to determine inotropic and chronotropic effects of existing drugs and candidate chemicals directly on human heart muscle. The well-established inotropic and chronotropic effects of the calcium channel blocker (verapamil), the ß-adrenoceptor blocker (propranolol), the phosphodiesterase inhibitor (theophylline) and the Na(+)/K(+)-ATPase inhibitor (ouabain) were tested on spontaneously contracting strips of human atrium. With demonstrative tracings, we showed the negative inotropic and chronotropic effects of verapamil and propranolol, the positive inotropic and chronotropic effects of theophylline and the transient inotropic and tachyarrhythmic effects of ouabain on dobutamine-pretreated human atrial strips. By using this method the undetermined inotropic and chronotropic effects of any candidate compound can be evaluated directly on spontaneously contracting human atrial muscle. Furthermore, we demonstrated the advantages of using dobutamine instead of conventional electrical field stimulation in order to obtain stable and durable contractions of the atrial strips. In conclusion, we describe a new, simple, reliable, convenient and ethical method for investigating the inotropic and chronotropic effects of candidate drugs directly on human atrium tissue without the need for human test subjects.

The effect of rosiglitazone in the prevention of intra-abdominal adhesion formation in a rat uterine horn model.

BACKGROUND: Effects of rosiglitazone in the prevention of adhesion formation were evaluated. METHODS: Eighty Wistar albino rats were randomly grouped into eight equally sized groups. A 2-cm segment of the antimesenteric surface of the right uterine horn was traumatized to form a standardized lesion, using bipolar cautery. A dose-response study was performed with 0.1, 0.3, 1 and 3 mg/kg/day rosiglitazone. Fifteen days later, adhesions were evaluated clinically and histopathologically. A time-response study was performed with 1 mg/kg/day rosiglitazone (the minimum dose found to significantly affect adhesion formation). Rosiglitazone was given for 7 days post-operatively and results were compared with those of control and the 15-day group (time-response). In all these studies, rosiglitazone was orally administered 3 days before the operation and continued post-operatively. In two further experimental groups, rosiglitazone was only administered pre-operatively or post-operatively. RESULTS: Approximately 1 mg/kg/day rosiglitazone was found to reduce adhesion scores both clinically and histopathologically. Duration of treatment was also found to affect the extent of adhesion formation. However, giving rosiglitazone either just pre-operatively or post-operatively did not significantly reduce adhesion formation. CONCLUSION: Rosiglitazone with peroxisome proliferator-activated receptor (PPAR)-gamma agonist activity reduced the formation of i.p. adhesion possibly by reducing the initial inflammatory response and the subsequent exudation in this study.

The evaluation of sympathetic system-related contractile activity of the rat vas deferens after ligation and intra-abdominal placement of the testis.

OBJECTIVE: To evaluate the contractile response of the vas deferens in a model of stress, to determine any changes in sympathetic activity as a result of stress in the ipsilateral testis, which decreases blood flow to the contralateral testis. MATERIALS AND METHODS: The study comprised two groups of six rats each; group 1 underwent a sham operation, and in group 2 the right testis was placed into the abdominal cavity and the vas deferens ligated. After 30 days, the vasa deferentia were resected bilaterally and their isometric contractions recorded. Electrical-field stimulation (EFS) was applied through a pair of platinum electrodes and concentration-response curves constructed for noradrenaline at 37 degrees C and to a solution containing 80 mmol/L K+. RESULTS: The vasa deferentia in both groups showed similar contractile responses to EFS, which were frequency-dependent and maximal at 80 Hz. Noradrenaline-induced contractile activity was lower in amplitude in the vasa deferentia of group 2 than in the contralateral and ipsilateral vasa deferentia of group 1, which were not significantly different from each other. All groups responded similarly to high K+. CONCLUSION: Intra-abdominal placement of the testes with vas deferens ligation decreased the contractile response to noradrenaline in the ipsilateral vas deferens without altering the contractile response to EFS and high K+. This difference could be caused by a reduction in the number of postjunctional alpha-adrenergic receptors or decreased receptor sensitivity. Both possibilities suggest that the vas deferens may initiate sympathetic activity, which may be responsible for contralateral testicular deterioration.