Page 147 - Cardiac Nursing

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C HAPTER 5 / Atherosclerosis, Inflammation, and Acute Coronary Syndrome 123
year. 16,236 More than 16 million Americans had a history of my- maintaining homeostasis of myocardial cells. Phosphate produc-
3
ocardial infarction or experienced angina pectoris in 2000. Ap- tion is markedly reduced. Intracellular hydrogen ions and lactic
proximately every 1 minute, an American dies from a coronary acid accumulate. Within a few minutes, ultrastructural changes
event. In developed countries, the number of coronary events par- can be seen, including cell swelling and depletion of glycolic stores.
allels the number of coronary events in the United States. The combination of hypoxia, reduced energy reserves, and acido-
25
Racial and gender variations exist in the incidence, prevalence, sis further hampers left ventricular function. Myocardial cells re-
presentations, and treatment responses. 7,228 Blacks have higher mor- main viable for at least 20 minutes. After 20 minutes, irreversible
41
bidity and mortality rates from myocardial ischemia and they also injury begins to occur. The actual events leading to cell death are
have a higher incidence of hypertension, obesity, and metabolic syn- unknown. 237,238 It has been postulated that calcium overload may
drome. Their access to medical care often is delayed after a coronary be a contributing factor because of the activation of various pro-
event. Indian-Asians have twice the incidence of CHD than whites in teases and phospholipases. 21,22 The integrity of the sarcoplasmic
the United States. Asians tend to have higher levels of lipoprotein A. membrane is damaged by these enzymes, leading to eventual cell
People of Mediterranean descent have a much lower incidence of is- death. ATPases are impaired by anoxia, which results in the pro-
chemic heart disease. The incidence of ischemic heart disease is equal duction of superoxides and hydrogen peroxide, both of which are
in men and postmenopausal women. Older adults experience higher highly diffusible and induce cell damage. 239 In addition, oxidative
mortality and morbidity from ischemic heart disease and have more stress causes a repertoire of cellular defenses to emerge. Ischemia
complications from multiple therapeutic interventions. can lead to endogenous antioxidant factors to modulate injury by
enzymatic pathways of cellular signals, which may determine the
Cellular Mechanisms and Events outcome of injury. 240 For example, mitogen-activated protein ki-
Caused by Myocardial Ischemia nase and nuclear factor- B inhibit injury and signal ICAM-1 to
241,242
mediate injury.
Myocardial ischemia develops if blood flow containing oxygen- Ischemic preconditioning, which refers to a state in which tis-
rich nutrients is insufficient in meeting metabolic demands of the sue is rendered resistant to deleterious prolonged ischemia and
myocardial cells. Consequences of myocardial ischemia are de- reperfusion before exposure of vascular occlusion, may be critical
picted in Figure 5-5. Oxygen deprivation of the tissues caused by in determining the extent of injury that myocardial cells can sus-
diminished blood flow can cause ischemia within 10 seconds. 21 tain. Activation of adenosine receptors and protein kinase is es-
Myocardial oxygen reserves are used within 8 seconds. Myocardial sential to this preconditioning. A cascade of events including
function and contractility become profoundly depressed within 1 postischemic leukocyte rolling, which leads to adhesion and em-
minute. The myocardium shifts from aerobic metabolism to anaer- igration, is dependent on expression of p-selectin on venular en-
obic metabolism through the glycolic pathway. Glycolysis can sup- dothelium. 243 Another factor affecting endothelium may be the
ply only 65% to 70% of the total myocardial energy requirement. reduction in L-arginine availability, which has been identified
A
A
Anaerobic glycolysis will generate some ATP but is insufficient in with impairment of endothelium-dependent, nitric oxide-medi-
ated vasodilation by ischemia–reperfusion. 244 Downregulation of
endothelial nitric oxide synthase may lead to the inability of
arginase blockage or L-argine supple mentation to completely re-
MYOCARDIAL ISCHEMIA store vasodilatory function. In addition, activation of peroxisome
proliferatory-activated receptor , which regulates genes of my-
ocardial fatty acid oxidation, may exhibit cardioprotection
through metabolic mechanisms. 245
Inadequate supply of Accumulation of
oxygen and nutrients waste products Restoration of oxygenated blood to the previously ischemic
myocardium is called reperfusion. 6,8 Occlusion of coronary blood
ATP
vessel followed by a sudden release is called coronary reactive hy-
Anaerobic peremia. 246 Reperfusion of a tissue bed results in reversal of is-
metabolism Inflammatory chemia but also releases toxic free radicals and an overabundance
mediators of calcium. Although reperfusion is absolutely necessary to restor-
intracellular H +
pyruvate Granulocyte ing cellular homeostasis, there are also detrimental effects that can
lactate activation result. 41 Myocardial stunning is a diminished contractile state in
Inhibition of Oxygen free the noninfarcted myocardium from excess production of free rad-
4,25
ion pumps radicals icals. Reperfusion arrhythmias are observed and are believed to
be caused by myocardial cells that were fatally damaged by the
intracellular Na + previous ischemic event.
extracellular K + The hemodynamic effects of myocardial ischemia are reduced
intracellular Ca ++
contractility and abnormal wall motion in the area of ischemia.
Changes in wall compliance and stiffness are affected, thereby re-
Altered membrane potential ducing cardiac output and stroke volume. Because of reduced
Cell edema
emptying of the left ventricle, pressures within the heart become
elevated. Pulmonary artery wedge pressure and left ventricular
end-diastolic pressure rise. Sympathetic compensatory mecha-
Failure of
Arrhythmias Cell death
contraction nisms respond to the decreased myocardial function. Blood pres-
sure and heart rate increase. A decreased blood pressure indicates
■ Figure 5-5 Consequences of ischemia. a large area of myocardial ischemia or vasovagal response. 3