Ventricular fibrillation (VF) was electrically induced in cats, rabbits, guinea pigs and rats. In young animals of all species and also in old rats short transient VF (TVF) was followed by spontaneous reversion to normal sinus rhythm. Old cats, rabbits and guinea pigs had episodes of sustained VF (SVF) which did not terminate spontaneously; artificial electro-defibrillation was required. Dibenzepin converted the sustained response of old animals to a transient one. Verapamil antagonized the effect of dibenzepin in old animals and also changed the TVF in young animals to SVF. The effect of calcie age of the animal is an important factor in determining whether the fibrillatory red to an alteration in the properties of the cell membrane.
In previous studies we hypothesized that spontaneous termination of ventricular fibrillation (TVF) requires a high cardiac catecholamine level ([CA]) during VF. During VF, sympathetic activity is enhanced but in the majority of cases [CA] does not reach the level required for self-defibrillation, most likely due to their relatively high reuptake by sympathetic nerve terminals. One possibility of obtaining TVF is by elevation of the [CA] during VF, either by catecholamine intracoronary injection or by treatment with compounds that inhibit catecholamine reuptake. To examine this assumption, we studied the effect of VF on 3 closely related compounds: talopram, talsupram and citalopram, with norepinephrine uptake inhibition (IC50NE) of 2.9, 0.79 and 8800 and dopamine (DA) uptake inhibition (IC50DA) of 44000, 9300 and 41000, respectively, as well as 2 enantiomers of a cis-1-piperazino-3-phenylindan derivative (Lu20-037 and Lu20-036) with IC50NE of 2.5 and 910 and IC50DA of 2.3 and 1700, respectively. The results support our hypothesis relating the defibrillating effect of a compound to its IC50NE, while its inhibitory effect on DA uptake seems to conteract the NE effect.
The ß-adrenergic receptor blocking properties of new open-chain and lactam-type benzamido analogs of practolol (2) were investigated. These compounds display a competitive blocking activity on both vascular and myocardial ß receptors. However, subtle structural changes in the aromatic moiety profoundly affected their organ specificity toward each of these receptors. Since all of the test compounds including practolol (2) share similar lipohydrophilic character, it may be concluded that their ability to selectively block either myocardial or vascular receptors depends primarily on electronic and steric factors.
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