adma, some of those airports definitely did have international flights in the past--St. Louis and earlier Kansas City were TWA hubs, New Orleans was a fairly significant hub for Latin America--but others never did. In general, though, there was much more international air service from the "heartland" two or three decades ago than today. That can only be a statement about demand. There are also a whole bunch of even bigger cities that have only seasonal service or only one flight (Cleveland, Pittsburgh, Cincinnati, Memphis, Denver, Portland).
Hydrogen: Sure, hubs play a role, but Canada has hubs as well. If there weren't demand for a 767 from Halifax to London every day (or Edmonton to London, for that matter) it wouldn't fly. Some of those cities I listed are also airline hubs, but they still don't have international service. Halifax doesn't serve as a hub beyond the Maritimes for Air Canada, and there are more people in St. Louis than in all of Atlantic Canada. It also doesn't explain the distinct lack of charters from any of these American cities.
Wonderboy: That doesn't explain cities like Edmonton which also has non-stop service to Europe even though it's not a hub, it has barely a million people, and it's far from any coast. Calgary has multiple flights every day year-round to Europe, even using larger aircraft like the 330s.
Another example: In 2008, Montreal had 4,466,400 passengers flying to international destinations not including the United States. By contrast, Philadelphia--a major hub and larger city--had 3,611,000, including Mexico and Canada. Even Boston, a larger city than Montreal that's usually considered a pretty worldly place, had only 3,808,000. More international passengers flew out of the Guam airport than out of Seattle.