The keepers knew almost as soon as they carried the giant panda cub from its mother Wednesday in a cooler filled with warm towels that something was wrong.

Even though the 4-day-old cub had seemed fine and had spent the night with the National Zoo’s female giant panda, Mei Xiang, it was clear that something had changed. The cub was lethargic, less vocal, and seemed to have trouble breathing.

Thus began, at 7:15 a.m. Wednesday, a frantic six-hour effort to save the life of one of the twin giant pandas born at the zoo on Saturday.

It ended, after veterinarians had given the cub oxygen, CPR and resuscitation drugs, and worked on it for minutes after its heart and respiration stopped.

Worldwide panda reproduction since 2008, visualized

“We kept going, and we kept listening, and then at 2:05, I said, ‘Sorry, guys, we’re done,’ ” the zoo’s chief veterinarian Don Neiffer said.

The death of the cub, whose sex was never determined, was a huge blow to the zoo, which had been overjoyed by the birth of giant panda twins — only the third time that had happened in a U.S. zoo.

“We were so in­cred­ibly hopeful,” Brandie Smith, the zoo’s associate director for animal care sciences, said Wednesday. “When we realized the cub wasn’t going to make it, it was devastating.”

Zoo director Dennis Kelly said: “This is a hard loss for us.”

It was second time in three years that the zoo has lost a panda cub shortly after birth. On Sept. 16, 2012, Mei Xiang gave birth to a cub with liver abnormalities, and it died six days later.

The cubs are extremely small and fragile when they are born.

The second twin and its mother were doing fine Wednesday, the zoo said.

Zoo officials expressed sadness over the death of one of Mei Xiang's cubs on Wednesday. The smaller of the two cubs was being cared for by a team around the clock after Mei Xiang rejected plans to swap the babies every four hours. (Reuters)

Weary staffers recounted the deceased cub’s last hours at the zoo Wednesday afternoon.

The cub had been born at 5:35 p.m. Saturday, weighing about three ounces. Its larger twin was born at 10:07 p.m. Saturday, weighing 4.8 ounces, the zoo said.

Keepers had been switching the cubs as often as they could — giving one to Mei, while caring for the other in a special incubator. Then, at an opportune time, they would swap the animals.

This gave each cub time with the mother and allowed her to focus on them individually. Often, when twins cubs are born, the mother is generally able to care for only one, and the other dies.

But it proved to be difficult to make the switch. The smaller cub wound up spending less time with the mother, and more time being cared for by the keepers.

Neiffer said it wasn’t that Mei preferred one over the other. She was equally attentive to whichever cub she had. “She was trying to do her best with both,” he said.

But the smaller cub seemed to suffer, regurgitating and not keeping on weight.

Neiffer said the staff was able to make a switch Tuesday afternoon and give the smaller cub to Mei. Before that, “the cub was noted to be strong and vocal,” he said.

Overnight all seemed well, he said. “The panda team . . . heard both cubs vocalizing, acting normal,” Neiffer said.

But when the morning swap was made, the smaller cub seemed to be in trouble, he said.

The team began administering antibiotics, fluids and nutrition, and pumping oxygen into the incubator.

Neiffer said it was unclear what, if anything, happened when the cub was with Mei overnight. He said it can be impossible to see the tiny cub tucked into the fur of its burly mother. “Mom’s able to literally hide it under her chin,” he said.

By midmorning, Neiffer said the cub seemed to improve. “At that point, the kid was coming up,” Neiffer said. “Slowly. Not great. But making some strides.”

Then about 12:30 p.m., Neiffer got a call that the cub seemed to be failing. He rushed to the panda house, where almost a dozen experts were crowded around the cub trying to save its life, he said.

About 2 p.m., the cub went into respiratory arrest and then cardiac arrest. Veterinarians did gentle cardiopulmonary resuscitation.

“We had our moments during that two hours where we said, ‘All right, we are going to get over this,’ ” Neiffer said.

But they could not.

“It was very quick,” he said of the animal’s death. “I don’t know how long the heart was beating after the baby stopped breathing. Probably not very long.”

“I made the call,” he said. “It’s part of the job. It’s not the fun part of the job. . . . It’s my burden, that I chose.”

Smith said that many of the country’s foremost panda experts, including a zookeeper from Zoo Atlanta who sped to Washington as soon as the National Zoo announced that Mei Xiang had had twins, were involved in the cub’s care. Experts in China advised the team by phone.

“We’ve all been awake since pretty much Saturday,” Smith said. “The entire panda house was filled with the best medical care team in the world. . . . We were so in­cred­ibly hopeful because we had that team.”

Ultimately, zookeepers do not know what caused the baby panda’s death, Neiffer said. They plan a necropsy, which may lead to better panda science.

“When we receive back our results from pa­thol­ogy, depending what they identify, it may alter the way we approach the next panda cub, and we will share that,” Neiffer said.

Before Saturday, Mei Xiang had delivered two surviving cubs since 2005 — Tai Shan on July 9, 2005, and Bao Bao on Aug. 23, 2013.

She gave birth to a stillborn cub about 26 hours after Bao Bao.