engleski

Apoptotic cell death and cardiovascular diseases ; clinical implications

Apoptotic cell death has been verified in various cardiovascular diseases. Ischemic conditions seem to be leading inducers of apoptotic cell death. In congestive heart failure apoptotic index was reported to be near 35%. In primary and restenotic atherosclerotic lesions apoptotic cell death was also detected. During coronary artery bypass grafting procedures, ischemic– reperfusion injury occurred regardless of the method of intraoperative myocardial management, however we presume that apoptotic index varies depending of the method of intraoperative myocardial management. The apoptosis reduction appears to be the main goal and possibly the therapeutic target, and in the course of treatment two main approaches should be realized. First, reduction of the cardiac response on ischemic– reperfusion injury, and decreasing of the systemic inflammatory response to cardiopulmonary bypass is favored using “ off pump surgery” and, or, ischemic preconditioning which demonstrated to decrease infarct size, reduces postoperative arrhythmias, reduces ATP depletion in group of patients with “ off pump” and “ on pump” coronary artery surgery. We propose study designed in way that myocardial biopsies should be removed in patients undergoing CABG in the period before cardiopulmonary bypass is established, second samples should be removed after cross clamping period, and third after 20 min of reperfusion. Patients should have different methods of myocardial management. Group of patients with “ off pump” surgery, should be compared with patients conventionally operated. Such designed study could explain impact of ischemic and reperfusion injury, to reveal impact of systemic inflammatory response and hypothermia on myocardial apoptosis. Second approach is pharmacological. In reduction of ischemic– reperfusion injury, calcium channel blockers could be added in priming volume of cardiopulmonary bypass or in cardioplegic solutions. In patients with heart failure compensatory mechanism with increased sympathetic nerve activity promote apoptotic cell death. Medicaments such as ACE inhibitors, angiotenzin II blockers and beta adrenergic blockers decrease rate of apoptosis in myocardial tissue. Avoiding of catecholamines in patients with cardiogenic shock and postoperative low cardiac output syndrome, seems to be benefitial, phosphodiesterase inhibitors should be recommended. Use of intraaortal ballon pump should be more often in these patients, indications for use should be wider. Long term antiapoptotic medical therapy is crucial for patients with ischemic heart disease, taking into account that in restenotic lesions apoptotic index is near 70%. Considering all these facts and hypotheses, we can conclude that patients could have therapeutic benefit with synthesis of these approaches.

apoptosis; cell death; cardiovascular disease; heart surgery

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