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The channels of the heart

A UNIFESP team identifies the interaction between heartbeats and cardiac contraction, mediated by calcium

HÉLIO DE ALMEIDAThe calcium present in blood circulation plays a paramount role in an event that repeats itself, with varied vigor, hundreds of thousands of times per day. The capacity for cardiac muscle contraction is regulated by the quantity of calcium in the interior of its cells, whose supply depends on the calcium channels located on the cell membrane. An example: as you increase the number of heartbeats, the membrane channels open up and allow more calcium to get in. The stretching of the muscle also sets off a chain of events that increase the contraction capacity. Substances are released that augment the entrance of sodium into the cells – and a protein in the membrane promotes the exchange of excess sodium for calcium.

Some three decades ago, the cardiologist Paulo José Ferreira Tucci, a professor at the Physiology Department of the Federal University of São Paulo (UNIFESP), began to study the origins of the complex chain of mechanisms that regulate the passage of calcium. One of them that Tucci demonstrated during the 80’s, has to do with the increase of sensitivity to calcium of the heart’s contracting proteins always when the muscle is stretched.

Recently the group, led by Tucci, returned to directing their research towards the biochemical phenomena that make the myocardium contract and pulse. Making use of an isolated dog heart, fed by the blood of another dog, it was possible to evaluate the interaction between two of these events mediated by calcium, the stretching of the muscle and the increase of cardiac frequency. It was concluded that elevated cardiac frequency intensifies the organ’s response to stretching. The experiment’s preparation took some hours and demanded surgeries on both dogs. First the heart was removed from one of the dogs. Within this isolated heart a sac was installed that evaluated its contracting capacity and the pressure generated in its interior during the cardiac contraction. On the other side there is the second dog, whose function is to provide arterial blood for the isolated heart and receive it back again. “One of the merits of the work was to evaluate, under a physiological condition – the heart integrated to an intact system – the interaction between factors that previously had been studied in isolation and under very artificial experimental conditions”, says Tucci.

In another study the UNIFESP team analyzed the working of these mechanisms when the heart’s blood flow diminishes – in a situation of ischemia equivalent to that of chest angina, the sharp pain caused by the constriction of the artery. When the flow is re-established the working of the heart takes some hours to return to normal. During this critical phase there is the risk of serious complications, such as the accumulation of liquid in the lungs. The study concluded that, during the period of stupor, the response of the heart to constriction and to an increase of frequency is not affected.

The importance of these studies is not simply measured by their individual findings. The contraction of the muscle and the increase in heartbeats are mechanisms that allow the heart to rapidly adjust itself to the organism’s demands. A sprinter manages to increase, by a factor of five, his heart’s performance during a 100 meter sprint race. “In victims of chronic cardiopathy, the functioning of such mechanisms is jeopardized and doctors have no ways of therapeutically interfering in them”, says Tucci. The research aimed to widen the understanding of such factors in cardiac illnesses.

In another line of investigation, Paulo Tucci is verifying a theory that sounds paradoxical – small hearts beat better. Studies carried out on rats with clogged hearts revealed that the myocardium gained capacity in pumping after a piece of the left ventricle, necrosed by the clogging, was removed and the chamber remained with a smaller size. “Mathematically, this is easy to prove: the force to be generated by the myocardium is directly proportional to the relationship: cavity radius divided by the wall thickness. The greater the cavity size, the more difficult it is to generate pressure”, says Tucci. In the 90’s, this principle was applied to human beings. The removal of up to 30% of the hypertrophied heart, a strategy developed by the heart surgeon Randas Batista, from the state of Paraná, devolved quality of life to hundreds of patients with serious cardiac insufficiency, which had impeded them from walking or from making any sort of physical effort.

Doctors throughout the world have tested it. The smaller cavity confers to the myocardium, even when debilitated, a more adequate performance. In spite of the immediate benefits and the initial enthusiasm, the technique, known as ventriculoplasty reducer, was practically abandoned. In the medium and long term, its effects on mortality showed themselves to be frustrating.

A benefit in cavity reduction is observed in another situation of practical medicine: the removal of large scars produced by a myocardial infarction, a situation known as aneurysm of the left ventricle. The removal of the scarring is unanimously accepted as advantageous for the evolution of the sick patients. For this reason, in Tucci’s evaluation,  the problem might not lie in the Randas Batista technique, but in its application on patients at a very serious stage of cardiac insufficiency. “The results will possibly be different if the reduction were to be applied to patients with a dilated heart but still with its functions preserved”, he suggests. The work of operating the miniscule clogged hearts of the rats was the responsibility of Rosemeire Kanashiro, who today is carrying out her post-doctoral work at a hospital in Baltimore, United States.

The heart’s resistance is greater than had been imagined, as testified to in research carried out on rats which had had an infarct and submitted to malnutrition. The conclusion was the following: although they had been submitted to a scheme of protein and calorie restriction six weeks before the infarct and three weeks after it, they did not suffer a depression in their capacity of myocardium contraction. During the period of scarring there is a cardiac overload caused by the heart attack. As well as this, protein synthesis in the heart increases considerably. In spite of this, there was no jeopardizing of the working of the cardiac muscle. This study corroborated the concept of the existence of a hierarchy of importance of some of the organism’s systems. The heart and the brain are saved in situations of the deprivation of food.

The Project
Physiology and physiopathology in cardiology (99/04533-4); Modality Thematic project; Coordinator Paulo José Ferreira Tucci – Physiology Department, UNIFESP; Investment
R$ 1,006,278.24