World number one Nadal experienced problems with his troublesome right knee earlier in the tournament, but was nevertheless able to come through an epic five-setter with Dominic Thiem in the quarter-finals.
However, his condition notably deteriorated against Del Potro and a medical timeout early in the second set failed to bring the desired results for the Spaniard as he ended the contest trailing 7-6 (7-3) 6-2.
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