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Zadnipryany I.V., Professor of Normal human anatomy department,
Sataieva T.P., PhD of Medical biology department
Crimea State Medical University
Simferopol, Ukraine
Stunned and Hibernating
Myocardium
Both the hibernating and the stunned myocardium are characterized by
reversible contractile dysfunction. In hibernating myocardium ischaemia is
still ongoing, whereas in stunned myocardium blood flow is fully or almost
fully restored. Both the hibernating and the stunned myocardium retain an
inotropic reserve. In hibernating myocardium the increase in contractile
function is at the expense of metabolic recovery whereas in stunned myocardium
no metabolic deterioration occurs during inotropic stimulation. Therefore,
inotropic stimulation in combination with metabolic imaging may help not only
to identify viable, dysfunctional myocardium but also to distinguish between
hibernating and stunned myocardium. The therapy of hibernating myocardium is to
restore blood flow to the hypoperfused tissue. Myocardial stunning per se
requires no therapy at all, since by definition blood flow is normal and
contractile function will recover spontaneously. If, however, myocardial
stunning is severe, involves large parts of the left ventricle and thus impairs
global left ventricular function, it can be reversed with inotropic agents and
procedures. In the experimental setting, antioxidant agents, calcium
antagonists and ACE inhibitors attenuate stunning, most effectively when
administered before ischaemia [2, 4].
There are 2 major hypotheses for myocardial stunning: (1) a oxygen-free
radical hypothesis and (2) a calcium overload hypothesis. Postischemic
dysfunction may be due to cytotoxic oxygen-derived free radicals (ie, hydroxyl
radicals, superoxide anions) that are thought to be generated during occlusion
or, upon reperfusion. Such radicals cause lipid peroxidation, altering their
function and structure [1].
Normal cardiac contraction depends on the maintenance of calcium cycling
and homeostasis across the mitochondrial membrane and sarcoplasmic reticulum
during each cardiac cycle. Brief ischemia followed by reperfusion damages Ca2+
pump and ion channels of the sarcoplasmic reticulum. This results in the
electromechanical uncoupling of energy generation from contraction that characterizes
myocardial stunning. Calcium accumulates in the cell at the time of reperfusion
and that is followed by a partial failure of normal beat-to-beat calcium
cycling, which perhaps occurs at the level of the sarcoplasmic reticulum. This
mechanism is proposed to account for contractile dysfunction. Structurally,
myocytes in stunned myocardium appear normal when examined by light microscopy.
The appearance of glycogen vacuoles adjacent to mitochondria and of
myofibrillary loss are noted in most cases of hibernating myocardium when
examined by electron microscopy. Several controversies exist regarding these
histologic changes [1, 3].
Several animal models have been proposed to demonstrate the physiologic
significance of coronary stenosis, in which a regulation of flow and
downregulation of metabolism lead to hibernating myocardium. The key
determinant of this adaptive process is a reduction in the coronary perfusion
reserve that results from critical coronary stenosis [2, 5]. Conti demonstrated
that the production of an acute and critical reduction in coronary flow reserve
(CFR) in chronically instrumented pigs leads to an accelerated progression of
chronic stunning proceeding to hibernation in less than 2 weeks. The time frame
for the transition from stunning to hibernation can be fairly short, and it is
directly related to the degree of flow impairment in a stenotic coronary artery
that supplies the dysfunctional segment. As the ischemic threshold decreases
with a reduction in the CFR, repetitive stunning results in a delay in the
recovery of function that becomes longer than the interval between ischemic
episodes. The image below shows a schematic diagram of the potential mechanism
of myocardial stunning. Several other groups have also demonstrated impairment
of coronary vasodilator reserve in chronically dysfunctional myocardium. It has
been shown that in patients with CAD, flow reserve decreases as the degree of
stenosis is increased, and flow reserve is absent with stenoses as great as 80%
of the luminal diameter. Progression of coronary stenosis to a critical limit
and a loss of the CFR mean that subendocardial flow cannot accommodate the
increasing demand, predisposing myocardium to hibernation. Borderline
impairment with frequent intermittent ischemia when demand increases may
suffice to cause hibernation. Certainly, chronic resting ischemia causes
hibernation [1, 5].
Differentiating between subendocardial ischemia and hibernating
myocardium can be difficult. Collectively, these findings indicate that chronic
repetitive ischemia that progresses to hibernating myocardium is associated
with regional downregulation of the sarcoplasmic reticulum, with changes in
calcium regulation and gene expression. These changes are accompanied by modest
increases in myocyte apoptosis and a reduction in the regional myocyte nuclear
density. These same structural and functional findings occur in patients with
dilated cardiomyopathy of ischemic origin.
Литература
1. Cowan F. Outcome after intrapartum asphyxia in term
infants / F. Cowan // Semin. Neonatol. — 2000. — Vоl. 5. — № 2. — Р. 127 – 140.
2. Jennings R.B., Reimer K.A. Lethal myocardial
ischemic injury / R.B. Jennings, K.A. Reimer // Amer. J. Pathol. — 1982. — V.
122. — P. 219 – 231.
3. Jensen A. Dynamics of fetal circulatory responses
to hypoxia and asphyxia / A. Jensen, Y. Gamier, R. Berger // Eur. J. Obstet.
Gynecol. Reprod. Вiol. — 1999. — Vol. 84. — № 2. — Р. 155 – 172.
4. Wickline S.A., Lanza G.M. Molecular imaging,
targeted therapeutic and nanoscience / S.A. Wickline, G.M. Lanza // J. Cell
Biochem. — 2002. — Vol. 39. — P. 90-97.
5. Wickline S.A., Lanza G.M. Nanotechnology for
molecularimaging and target therapy / S.A. Wickline, G.M. Lanza // Circulation.
— 2003. — Vol. 107. — P. 10.
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