Size Matters
In my youth I lived and breathed to hunt. Started out with a Daisy bb gun at age six. Graduated to a .22 single shot at age 12. Back then there was no restrictions on youth having guns.
I don't have any idea how many big game animals I have killed, but it is considerable. Thousands of small game and varmints.
However, I have to say this; before you can kill or stop anything, you have to hit it, and it helps to hit it in the right spot. A bullet in the brain or spinal cord in the area of the neck will imediately bring the animal down. And it will almost always stay down, not even a twitch, just plop, down like dropping a wet dish rag.
I have also seen deer run 150 yards with a 30 cal hole through the heart.
That is why I like head shots. You don't have to chase the critter.
I have seen the lowly .22 LR take animals from the size of mice up to elk and 2000 lb. bulls. No doubt in my mind the small calibers can kill.
I have used a number of rifle calibers including .22 LR 22 Mag, 30-30, 222, 243, 30-06, 308, 270, 270 Weatherby Mag, 300 Mag.
I have killed many deer with one shot with the 222 to the head.
I have twice made a body shot on deer with the 222 and both times I wounded the animal and had to track it down The one was hit in the lungs, the other a little too low in the front shoulder. On the shoulder shot, the little pill stopped before getting into anything vital. Now hits like that with the 270 will usually go clear through and knock the deer down immediately. They won't usually get up. Of course the 222 delivers much more energy than the 45 auto. So see what you are up against?
If the animal is already spooked and moving out sometimes you can put a bullet through the heart or lung area and they will run a considerable distance before dropping from lack of blood. In other words if it was coming for you, it would get you before it died.
Though the light loads can kill, it quickly becomes evident that the more powerful loads are better for stopping and/or killing the animal. Absolutely no question about it. Size matters. It is a fact.
I have only owned 22 and 44 Spl revolvers. Let me just say that the 44 is very, very, much more effective, regardless what animal you may be after.
I have never shot at a man, nor do I want to, but I am sure that what I have learned about stopping animals will apply if needed.
My advice: what ever gun you decide to use, learn to shoot! Practice, practice, practice.