Page 36 - 82_01
P. 36
Coronary ischemia-reperfusion: role of nitric oxide and endothelin-1. A Review
produced vasodilatation, which was reduced by reactive patients were monitorized, and they were attendant by
blue 2, glibenclamide, and endothelin-1, but was not training of medical and nursing staff, providing trained
affected by L-NAME. After ischemia-reperfusion, the nurses with the authority and responsibility to perform this
vasodilatation to Ap4A diminished, and in this case the procedure, including external defibrillation, in the absence
relaxation to Ap4A was not modified by reactive blue 2, of a physician. Phase 3 (The Present): It is the phase of
L-NAME, glibenclamide, although it was reduced by myocardial reperfusion which was initiated in 1975 by
endothelin-1. These results suggest that the reduction of Chazov et al. who lysed coronary thrombi by infusing
the coronary relaxation to Ap4A after ischemia- streptokinase directly into the blocked coronary arteries of
reperfusion may be due to impaired effects of KATP patients with AMI (6), and it was demonstrated that timely
channels and to reduced response of purinergic P2Y reperfusion actually salvaged ischemic myocardium (213).
receptors (210). These three studies (208-210) also show During the last quarter century, myocardial reperfusion has
data suggesting that purinergic receptors may be a way been improved progressively by a number of key steps.
involved in the coronary response to some vasoactive However, although myocardial reperfusion represents a
substances and this way may be altered after ischemia- major advance in the treatment of myocardial infarction,
reperfusion. Interestingly, purinergic receptors may be also this procedure is often accompanied by myocardial injury,
involved in the coronary vasodilatation in response to Ach so that E. Braunwald and R. A. Kloner referred to
after ischemia-reperfusion, but not under control myocardial reperfusion as ‘a double-edged sword (10).
conditions. The role of purinergic receptors in the coronary Phase 4 (The Future): the prevention of myocardial
vasodilation in response to Ach may be developed in reperfusion injury. Many interventions to prevent or
coronary vasculature during ischemia-condition in order to diminish myocardial reperfusion injury have been studied
compensate the reduction of NO release in this condition (214). It has been estimated that timely, adequate
(211). reperfusion can salvage approximately 50% of severely
ischemic myocardium (215), and that prevention of
Summarizing, the data exposed before suggest that myocardial reperfusion injury should prevent the necrosis
ischemia-reperfusion alters the regulation of the coronary of an additional 40% (112). Nevertheless, further
circulation, which may be induced, in part, by experimental and clinical research on myocardial
dysfunction/damage of the endothelium. This alteration reperfusion injury should be carried out (9).
could lead to modification of the normal balance between
NO and ET-1 that exists under normal conditions for the The prognosis of AMI largely depends on its extent,
control of coronary vascular tone. After ischemia- and the final necrotic extent is mostly due to the speed of
reperfusion, the role of NO is reduced, whereas that of ET- the progression of ischemic injury and the duration of the
1 is augmented, which may have pernicious effects for the ischemia (215, 216). The most effective treatment to limit
functional capacity of coronary vasculature, as for example infarct size is early reperfusion, and the window in which
this vasculature could exhibit an exaggerated reperfusion effectively limits infarct size in patients with
vasoconstrictor and inflammatory response, thus ST segment elevation myocardial infarction is short. After
contributing to the presence of the non-reflow 3 h of ischemia, without collateral circulation and residual
phenomenon. Therefore, the damage of the endothelium, flow, the amount of salvaged myocardium is small or
with the consequent alteration in the interaction between nonexistent (217). Nonetheless, late reperfusion may be
NO and ET-1 may play a crucial role in pathophysiology also beneficial, and should generally be performed within
of disregulation of coronary circulation and of the non- 12 h of symptoms onset (218). In this case, however, the
reflow phenomenon after ischemia-reperfusion, and in benefit is due to the positive effects of reperfusion on
pathophysiology of reperfusion injury. Also, these two healing of myocardium damaged (218).
substances by forming a functional axis that acts on the
coronary artery wall, probably should be considered Protect patients against myocardial damage caused by
together in analyzing pathophysiology of myocardial ischemia-reperfusion has became a public health problem.
ischemia-reperfusion and reperfusion injury, as well as in Because the best strategies against the morbidity and
therapeutical approaches for mitigating reperfusion injury. mortality of AMI is to minimize the ischemic death of
myocardial tissue, there are a notable interest for
4. THERAPEUTICAL APPROACHES FOR investigating and learning how the heart can be protected
REPERFUSION INJURY from ischemic death. The development of new approaches,
including new techniques, as well as the discovery of
In an elegant article, E. Braunwald published that novel drugs could provide means for new ways of heart
during the last 100 years, approximately, the management protection against ischemic myocardial injury. About this
of AMI has gone through fourth major phases (9). These particular issue, several and revisions are available (9, 122-
phases are summarized as follows: The past: a) phase I: the 124, 217-220).
management was limited to bed rest, morphine for pain, as
well as digitalis, caloric and fluid restriction, and expectant A number of therapeutic strategies for preventing
treatment; b) phase 2: it began in 1961 with a paper by myocardial reperfusion injury have been developed. In
Desmond Julian, where he described what later would be general, they can be grouped in two ways: a) non-
known as the Coronary Care Unit (212). In these Units the pharmacological strategies (conditioning phenomena:
ischemic preconditioning (IPC), ischemic postconditioning
@Real Academia Nacional de Farmacia. Spain 35
