Key result
OPC 3911 increased peak force by 50.7%, and the addition of rolipram potentiated this effect to an 82.8% increase, likely via an increased second inward current.
Why the study?
Does OPC 3911 alone and in combination with rolipram alter inotropic and electrophysiological properties in isolated cardiac muscles and myocytes?
Does OPC 3911 alone and in combination with rolipram alter inotropic and electrophysiological properties in isolated cardiac muscles and myocytes?
Rolipram potentiates the inotropic effect of the PDE III inhibitor OPC 3911 in cardiac muscle, likely via an increased second inward current (Isi).
Answers are grounded in this paper and cite their sources.
Augments PDE inhibitor synergy data in isolated cardiac tissue; leaves open clinical translation from animal findings.
OPC 3911 is a potent inhibitor and PDE III is a specific inhibitor in cardiac muscle. The effects of the drug alone and in combination with the non-inotropic PDE IV inhibitor rolipram were analysed using hearts from guinea-pigs and ferrets. OPC 3911 had an EC50 value of 0.1 microM. At 0.1 microM peak force was increased by 50.7 +/- 7.6% (n = 6, P < 0.001), time to peak tension (TPT) reduced by 18.7 +/- 5.6% (n = 6, P < 0.05). Time to half relaxation (THR) was prolonged by 19 +/- 4.2% (n = 6, P < 0.001). After addition of rolipram (30 microM), there was a potentiation of peak force at all concentrations of OPC 3911. At 0.1 microM OPC rolipram increased peak force by 82.8 +/- 8.9% (n = 6, P < 0.001), reduced TPT by 73 +/- 6% (n = 6, P < 0.005) and increased THR by 27 +/- 5% (P < 0.01). OPC 3911 shortened action potential duration (APD) at 50% repolarization by 5.3 +/- 2.5% (n = 6, P < 0.05). Addition of rolipram prolonged APD by 3.7 +/- 2.5% (n = 6, P < 0.05). Second inward current (Isi) was increased at 3 microM OPC 3911 by 46 +/- 6% (n = 6, P < 0.05). The combination of OPC 3911 and rolipram intensified the Isi to 101 +/- 5% (n = 3). Rolipram slowed the rate of restitution and the onset of restitution was prolonged. Relative maximum post-extrasystolic potentiation was reduced in the presence of OPC 3911 from 67 +/- 5% to 45 +/- 6%. Adding rolipram caused potentiation of 55 +/- 6%. OPC 3911 increased the recirculation fraction of activator calcium from 0.36 to 0.42 (n = 10, P < 0.05). After addition of rolipram the recirculation fraction was 0.41 +/- 0.04 (n = 10, P < 0.05). The results suggest that rolipram exerts its potentiating effect on OPC 3911 via an increased Isi.
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Mörner et al. (1994) studied Cardiac muscle physiology. OPC 3911 alone and in combination with rolipram vs. OPC 3911 alone was evaluated on Peak force and second inward current. OPC 3911 increased peak force by 50.7%, and the addition of rolipram potentiated this effect to an 82.8% increase, likely via an increased second inward current.
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