Key result
In isolated dog heart preparations, PN 200-110 increased coronary blood flow at doses significantly lower than those required to decrease sinus rate, AV conduction, or ventricular contraction.
PN 200-110 demonstrates potent and selective coronary vasodilatory effects with significantly less impact on cardiac automaticity, conduction, and contractility in canine models.
May support selective coronary vasodilation research; leaves open translation from canine models to human disease.
Coronary vasodilator and cardiac effects of PN 200-110 were compared by use of isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. PN 200-110 was administered intraarterially. In all preparations PN 200-110 produced an increase in coronary blood flow. In SA node preparations, the drug produced a decrease in sinus rate and atrial standstill as well, but only in large doses. The dose that produced a 15% (nearly half-maximum) decrease in sinus rate was about three times the dose that doubled coronary blood flow. In AV node preparations, the drug produced an increase in AV conduction time and, in large doses, second- or third-degree AV block only when it was injected into the artery supplying the AV node. The dose that produced a 15% (nearly half-maximum) increase in AV conduction time was approximately 12 times the dose that doubled coronary blood flow. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. However, the dose that produced a 50% decrease in the force of contraction of the papillary muscle was approximately 14 times the dose that doubled coronary blood flow. These effects of PN 200-110 were of long duration. The drug was entirely ineffective in changing the rate of ventricular automaticity. The order of selectivity of PN 200-110 was as follows: coronary blood flow greater than SA nodal automaticity greater than AV nodal conduction greater than ventricular muscle contraction. This cardiovascular profile of PN 200-110 is slightly different from that of PY 108-068, a compound closely related to PN 200-110 in chemical structure.
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Wada et al. (1985) studied this question. PN 200-110 was evaluated on Coronary vasodilator and cardiac effects. In isolated dog heart preparations, PN 200-110 increased coronary blood flow at doses significantly lower than those required to decrease sinus rate, AV conduction, or ventricular contraction.
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