Preventing heart failure post attack in pigs

Published in The Hindu on February 21, 2013

A study published today (February 21) in Science Translational Medicine journal holds the promise that one day people who have suffered a heart attack (myocardial infarction) may not progress to a stage where the heart’s ability to pump blood to meet the body’s requirement gets compromised (heart failure).

A block in the coronary arteries can cut off oxygen supply to a part of the heart resulting in a heart attack. The cells of the heart that do not receive oxygen get permanently damaged. Since the damaged heart cells lack the capacity to regenerate, a thick scar develops. Unlike heart muscles, the scar tissue lacks the ability to contract and pump blood.

Building on their earlier work carried out on rats, the researchers from the University of California, San Diego induced an attack in the left ventricle and then injected a hydrogel, which is derived from a pig’s heart (myocardial extracellular matrix), into six pigs (test group). Four control pigs were given a saline injection. One of the control pigs died during the experiment.

It must be noted that the extracellular matrix is specific to each tissue. The basic function of the gel is to provide a scaffold for new cardiac cells to form. “A vast majority of transplanted stem cells die with the first 48 hours so they have limited ability to recruit new cells to the area. In contrast, our material is present for up to three weeks in the tissue and therefore can recruit many more cells,” Dr. Karen L. Christman noted in his email to this Correspondent. He is the senior author of the study and an Assistant Professor at University of California, San Diego.

Apart from testing the safety aspects of the gel, the researchers studied the ability of the gel to help the damaged heart recover and function like a healthy one.

The matrix was injected two weeks after the animals suffered a heart attack. According to them, injecting the matrix gel immediately after an infarct would have destroyed the purpose as the introduced matrix would have got degraded along with the native matrix that was getting destroyed.

To assess the heart’s condition, they checked all the heart parameters — ECG, ejection fraction (amount of blood pumped out with each contraction), and the amount of blood that remains in the ventricle after it contracts (end-systolic volume) and the amount of blood in the ventricle before it starts contracting (end-diastolic volume – EDV).

In patients who have suffered an attack, any increase in end-systolic volume indicates reduced heart contractibility. This is the reason why a continuous increase in ESV (end-systolic volume – ESV) was seen in the control pigs vis-a-vis the treatment group.

These parameters were measured for all the animals prior to inducing an attack, before injection and finally before killing the animals three months after the injection.

The results show great promise. Although no statistically significant differences were seen in all the three parameters – EF, ESV and EDV, there was significant difference between the two groups three months after injection. The EF (ejection fraction) improved very well in the treatment group and was quite comparable to before inducing an infarct. EF deteriorated in the control group.

Unlike in the control group, the end-systolic volume and end-diastolic volume reduced in the treatment group. Similarly, the infarct size improved in the treatment group than the control.

The animals killed three months after the injection were studied for signs of cardiac muscle improvement. Those that received the gel injection had “distinct bands of muscle along the endocardium;” the control group had “moderately thickened” endocardium and had “minimal muscle” formation. Also, the percentage of collagen (a major insoluble fibrous protein) in the infarct reduced in the pigs that received the gel.

Next, the safety aspects were studied. Tissue samples from major organs examined showed no difference in both the groups. It did not cause blood clotting when injected into rats.

It was also found to be biocompatible. The matrix injected into rats completely degraded by the 28th day. “As long as the cells are removed from the tissue, the remaining material is biocompatible [in humans],” Dr. Christman noted.

Finally, they tested the matrix’s compatibility with human blood, particularly the clotting time and platelet activation. Platelet activation was seen only when “high” concentrations (2.5 times the normal value) of gel were introduced into the blood.

“These data in a large animals show that the [material] not only improves functional outcome after a heart attack but is also safe,” notes the Editor’s summary. “The material [is] ready to move toward clinical tests in people.”