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Heart Conditioning
Coronary arteries are the blood vessels of the heart. Myocardial ischemia or infarction occurs when blood supply to the heart
muscle (myocardium) is reduced or stopped due topartial or complete occlusion of the coronary arteries, leading to injury or death
of the myocardium, respectively.
In coronary artery disease (also called ischemic heart disease), there is coronary occlusion leading to myocardial (heart) ischemia.
Mild, transient, physiological heart ischemia produces adaptive or compensatory mechanisms. Severe, sustained, pathophysiological heart ischemia
gives rise to maladaptive or decompensatory mechanisms. Both compensatory and decompensatorymechanisms lead to neurohormonal activation,
heart remodeling, and other eventssuch as oxidative stress, autophagy (a cellular process to remove wastedcellular materials so as to maintain
cellular homeostasis), endothelin, nitricoxide, inflammatory mediators, growth factors etc.
Activation of the sympathetic nervous system and the rennin-angiotensin-aldosterone system is the main neurohormonal activation
Mild, transient and physiological activation of the sympathetic nervous system leads to accelerated heart rate, heartcontractility and
cardiac (heart) output. However, severe, sustained and pathophysiological activation of the sympathetic nervous system has
detrimental effects on heart cell biology, leading to loss of cardiac (heart) function. Physiological activation of the
rennin-angiotensin-aldosterone system results in constriction of blood vessels, cell growth, secretion of a hormone called aldosterone,
catecholamine release, which keep short-term cardiovascular homeostasis. Pathophysiological activation of the
rennin-angiotensin-aldosterone system is maladaptive, resulting in fibrosis (formation of fibrous tissue) of the heart ,kidney and other
organs, contributing to decreased vascular (blood vessel) compliance and increased heart ventricular stiffness. Thus, compensatory
activation of the sympatheticnervous system and the rennin-angiotensin-aldosterone system improve heart output through increased
retention of salt and water, peripheral arterialconstriction, increased heart contractility, and activation of inflammatory mediators
involved in heart repair and remodeling.
Heart remodeling affects the biology of the heart cell, and the geometry and architecture of the heart, as a response to
physiological or pathophysiological heart ischemia. In compensatory mechanisms, heart hypertrophy reduces the increased tension
of the heart and helps maintain heart output and cardiovascular function, which is essentially beneficial and improves heart
muscular economy. In decompensatory mechanisms, heart remodeling is characterized by progressive heart dilatation,
heart hypertrophy, fibrosis and deterioration of heart performance.
Reactive oxygen species (ROS) are a normal byproduct of aerobic metabolism. In the heart, ROS can modulate the activity
of a variety of intracellular proteins and signaling (inducing) pathways, including essential proteins involved in heart contractility
such as ion channels and muscle proteins, as well as signaling pathways involved in heart cell growth. Oxidative stress in the
heart may be due to decreased antioxidant ability or the increased production of ROS secondary to mechanical strain of the heart,
neurohormonal activation, or inflammatory cytokines (mediators for inflammatory and immune responses, such as tumor
necrosis factor, interleukin IL-1). Excessive ROS in the heart result in contractile dysfunction, stimulate heart cell hypertrophy and
apoptosis (programmed cell death), increase proliferation of fibrosis and collagen synthesis and stimulate increased matrix
metalloproteinase (enzyme that cleaves extracellular proteins) abundance and activation.
Thus, mild, transient, physiological myocardial ischemia which is a stress to the heart, can initiate compensatory adaptations,
which maintain cardiovascular homeostasis and normal cardiovascular function, at the molecular, cellular, structural, tissue and organ levels.
In 1986, Murry et.al. first demonstrated ischemic preconditioning in dogs. Brief (5-minute) repeated occlusions of the coronary artery
before the subsequent sustained occlusion resulted in reduction in infarct size. I have also observed that single brief (5-minute) ischemia
followed by sustained ischemia reduced the subsequent ischemia-reperfusion induced cardiac arrhythmias and decreased contractility in
the isolated rat heart (unpublished data, 1986). It is well-established that ischemic preconditioning is a two-phase phenomenon with a
first window of protection occurring within minutes of a mild ischemic insult lasting only 1 to 2 hours and a second window of
protection exhibiting between 12 and 24 hours and lasting for 3 to 4 days. The mechanisms of the two windows of ischemic preconditioning
are not the same. The first phase is due to quick modification of pre-existing proteins, the second phase needs formation of new proteins.
It appears that the beneficial and protective effects within the second window is as powerful as that of the first window of protection.
Ischemic preconditioning has been reproducibly well established in all animal species investigated as well as humans. Ischemic
preconditioning is beneficial and protective against postischemic contractile dysfunction, ischemia- and reperfusion-induced cardiac
arrhythmias, apoptosis , and infarct injury. This shift of the heart to a preconditioned phenotype (feature) with mild, transient,
physiological heart ischemia is recognized as an important progress in the field of heart protection.
Ischemic preconditioning with mild coronary occlusion and reperfusion before a sustained period of coronary occlusion with
reperfusion reduces the ischemia-reperfusion injury. Ischemic postconditioning with repetitive mild coronary occlusion during early
reperfusion of myocardial infarction decreases infarct size. Remote ischemic preconditioning with mild ischemia and reperfusion of a
distant organ protects the heart. These conditioning protocols comprise a complex signal cascade of cell membrane receptor activation,
intracellular enzyme activation, and inhibition of death signaling (inducing) in mitochondria.
It is likely that ischemic preconditioning occurs naturally in humans. Pre-infarct angina (chest pain) may resemble ischemic
preconditioning. Patients who had previous angina or chest pain that appeared prior to myocardial infarction had lower in-hospital
death, severe heart failure or shock. The beneficial and protective effects of pre-infarct angina may be due to ischemic preconditioning.
Ischemic conditioning has been utilized in patients with coronary artery disease. Ischemic preconditioning improved clinical outcomes
in patients undergoing cardiac catheterization and heart surgery. Ischemic postconditioning decreased infarct size and other measures
of reperfusion injury in patients with myocardial infarction.
Ischemic remote conditioning generally uses intermittent inflation of a standard blood pressure cuff to 200mmHg, with three to four
5-minute inflations separated by 5- minute reperfusion periods. In patients undergoing cardiac catheterization or heart surgery,
remote heart conditioning decreased heart injury and major adverse heart and cerebrovascular events. Moreover, remote preconditioning
and postconditioning was found to be effective in decreasing stroke severity in animal studies.
Instead of using heart ischemia, pharmacological conditioning (preconditioning mimetic) makes use of a pharmacological agent for
protection against ischemia-reperfusion injury. Several drugs that mostly play a role in the mechanism of ischemia-reperfusion injury
were investigated, such as adenosine, nicorandil, erythropoietin, diazoxide, cyclosporine. However, the outcomes are disappointing.
At present, ischemic conditioning is more powerful compared with that of pharmacological conditioning.
An abundance of cardioprotective signaling (inducing) biochemical events have been identified in heart ischemia. There are three
levels of signal transduction (propagation) : triggers, intracellular mediator cascade and effectors. Triggers are molecules like adenosine,
bradykinin, opioids that are formed and released from heart cell during heart ischemia. This cell membrane receptor activation initiates
intracellular cascade of enzyme, mostly protein kinase, which acts on the effectors such as mitochondria or cytoskeleton that stabilize the
jeopardized heart cell and prevent heart cell death. Nitric oxide, protein kinase activation and mitochondria seem to be important elements
in all forms and signal pathway of heart protection involved in ischemic conditioning.
Heart conditioning is an effective method of inducing heart protection, as it is both safe and easily feasible. Remote ischemic
preconditioning protocols use arm or leg ischemia and reperfusion rather than coronary artery manipulation. Exercise is an independent
factor in heart protection. It decreases cardiovascular risk by increasing fat metabolism, reducing obesity and increasing insulin sensitivity.
Exercise protocols can initiate ischemic preconditioning, and decrease ischemic injury during cardiac catheterization. Nitric oxide is an
initiator and mediator of ischemic preconditioning. The intravenous administration of nitric oxide donor, nitroglycerin, has been found
to protect human heart against heart ischemia.
To recapitulate, by mild, transient, physiological heart ischemia, which is a stress to the heart, compensatory adaptations are induced,
which maintain cardiovascular homeostasis and normal cardiovascular functions, at the molecular, cellular, structural, tissue and organ
levels. Therefore, the heart can already be conditioned and protected, as demonstrated by the beneficial and protective effects observed
following the subsequent sustained heart ischemia and/or reperfusion. The heart then becomes less vulnerable to subsequent cardiovascular
events. Heart conditioning is thus the most important healthy regimen, because it can prevent the most common but fatal diseases of
sudden death, myocardial infarction and stroke, at least reduce the morbidityand mortality. Besides, a healthy cardiovascular system covers
and crosstalks to all other systems of our body. Heart conditioning not only has protective effects on the heart, but also remote organs
such as brain,lung, kidney or gut, against injuries associated with ischemia and other insults, including toxicants, hemorrhagic
shock/resuscitation, and iodinated radiocontrast media. Moreover, it is speculated that, similar to heart conditioning, the other body systems
may likewise be stressed, conditioned and protected. Hence, evidence that conditioning exists in humans may provide a major impetus
to the development ofmodalities or measures for keeping the heart and the other body systems in a continuously conditioned and protected
state, preferably regularly and indefinitely. The response of the body to environmental changes is the fundamental of homeostasis.
The human body is capable to recruit various adaptive, compensatory mechanisms in order to keep body homeostasis and normal function
in response to a variety of aggressions or stressors. It is becoming increasingly clear that conditioning of the heart and other body systems
are stressors which can elicit compensatory adaptations so as to maintain cardiovascular and body homeostasis, and is an important feature
of successful antiaging programs.
You can buy a healthy sphygmomanometer (www.heartdisease.idv.tw) to perform heart conditioning.
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