Off idle stumble and misfire at WOT (or near WOT - like 3/4 throttle) that is not attributable to a fuel/air issue is often caused by erratic timing advance.
Check your distributor for sticking weights, weak or broken springs and worn pivot points (either the pins or their locating holes).
Remember, the vacuum advance is in control of your timing when the throttle is closed (or nearly closed - like feathering it out) and it gradually gives up that control to the mechanical advance as the throttle opens toward WOT.
A sticking mechanical advance system won't advance the spark quickly enough when called upon. It might catch up eventually. Or, as you have noticed, if you let off the gas - the vacuum advance will take back control and power immediately returns.
The vacuum advance system is primarily there to increase fuel economy. The mechanical advance is there to advance the timing as quickly as possible - to crank the engine up when you need it.
Not saying this is going to be your answer (esp with a 6 month old distributor) but it might be worth checking out.
4500 RPM - Dude! Unless you have modified your intake (and exhaust) a 350 can barely breathe that fast.