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272 PART 3: Cardiovascular Disorders

metalloproteinases and replacement with fibrous connective tissue leads S100A8/A9, HMGB1) bind innate immune Toll-like receptors. Once
to remodeling and decreased contractility. 24,27 Increased levels of circu- triggered, Toll-like receptors signal through NF-κB and other pathways
lating renin, angiotensin II, endothelin, and norepinephrine promote to increase expression of inflammatory cytokines, cell surface adhesion
cardiomyocyte hypertrophy, apoptosis, myocardial fibrosis, and vascular molecules, calcium channel binding proteins like S100A8/A8, reactive
cell hypertrophy. Myocardial norepinephrine stores are depleted and oxygen radicals, and nitric oxide; all of which can contribute to decreased
β-receptor density is reduced in chronic dilated cardiomyopathy. 25,27,28 ventricular contractility. Coronary capillary endothelial activation,
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Biochemical changes that may contribute to decreased contractility damage, and dysfunction also contribute, in part due to impaired regu-
include decreased efficiency of the sarcoplasmic reticulum calcium lation of coronary microvascular blood flow, which impairs myocardial
pump, decreased actin-myosin adenosine triphosphatase activity, and oxygen extraction, and in part due to edemagenesis. Thus, multiple
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change in myosin isoenzyme composition. pathways of the intramyocardial inflammatory response may contribute
to myocardial dysfunction following myocardial ischemia-reperfusion
Acute Causes: In the ICU, acute causes of decreased left ventricular or during noncardiac systemic inflammation and sepsis.
contractility are important because the acute causes are potentially Septic myocardial dysfunction includes systolic and diastolic abnor-
reversible (Table 35-2). Acute causes of depressed left ventricular malities, is associated with increased CK and troponin levels, and con-
contractility include ischemia, exogenous toxins such as alcohol tributes to adverse outcome of sepsis. Cardiac dysfunction can occur
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and drugs, and an intramyocardial inflammatory response follow- during noninfectious systemic inflammation and anaphylactic shock.
7
ing ischemia-reperfusion or due to inflammatory mediators of sep- Hyperthermia and hypothermia may decrease myocardial contractility
sis or systemic inflammation. In addition hypoxemia, respiratory and contribute to depressed left ventricular function observed during
acidosis, metabolic acidosis, ionized hypocalcemia, and hypo- and sepsis and other critical illnesses associated with marked abnormalities
hyperthermia may contribute. of body temperature (see Chaps. 64 and 131).
Myocardial Ischemia Transient ischemic episodes occur frequently in criti-
cally ill patients. The onset of ischemia is due to myocardial oxygen Myocardial Hypoxia In the absence of coronary artery disease, critically ill
demand exceeding the ability of the myocardium to extract oxygen from patients with sepsis may also manifest global heterogeneous left ventricu-
the oxygen supply (coronary blood flow multiplied by arterial oxygen lar hypoxia with increased creatine kinase MB and troponin levels. The
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content). Myocardial oxygen demand is increased by increasing heart heart consumes less lactic acid and may produce lactic acid. If inadequate
rate, contractility, afterload, preload, and the basal metabolic rate of oxygen delivery in relation to demand is not corrected quickly, then
the myocardium (which increases with increased sympathetic tone and the heart may enter a detrimental positive-feedback loop of decreasing
catecholamines). Many of the underlying illnesses encountered in the contractility, decreasing cardiac output and coronary perfusion, and,
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35
critically ill and many of the therapies, including fluid and inotropic or hence, decreasing contractility leading to precipitous cardiac arrest.
vasoactive drug infusion, contribute to markedly increased myocardial In the canine model, this vicious cycle occurred when arterial O saturation
2
oxygen demand. Because of the prevalence of coronary artery disease decreased below 75% (arterial partial pressure of O = 40 mm Hg) when
2
in older patient populations, ischemia in the ICU is frequently regional hemoglobin concentration was 14 g/dL. Accordingly, aggressive measures
with associated wall motion abnormalities. Accordingly, a high index to prevent this level of hypoxemia by keeping arterial O saturation
2
of suspicion and an early aggressive diagnostic approach are indicated above 85% to 90% are indicated; maintaining a reasonable hematocrit in
and facilitate the early treatment of ischemic coronary artery disease, as hypoxic critically ill patients with risks for myocardial ischemia is part
discussed in more detail in Chap. 37. of this therapy.
Side Effects of Common Drugs Exogenous toxins may result in acutely depressed Myocardial Acidosis Respiratory acidosis results in myocardial intracellular
myocardial contractility. Ethanol is a commonly encountered substance acidosis, and intracellular acidosis decreases the effect of intracellular
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that acutely depresses contractility. Drugs commonly used in the ICU that calcium on the contractile proteins so that contractility is decreased. In
significantly depress contractility include β-blockers, calcium channel critically ill patients, respiratory acidosis may significantly contribute to
blockers, and antiarrhythmics such as disopyramide and procainamide. depressed contractility and reduced cardiac output at partial pressure of
37
Therapeutic approaches to treating drug toxicity is specific for each drug CO (P CO 2 ) levels of 60 mm Hg and certainly by P CO 2 levels of 90 mm Hg.
2
(Chap. 124) while infusion of intralipid is a general adjunctive approach These considerations may be particularly important in patients in whom
to alter the distribution and immediate toxicity of lipid-soluble toxins. 30 the clinician actually seeks a high P CO 2 during mechanical ventilation
Inflammatory Response An intramyocardial inflammatory response can be (permissive hypercapnia) to minimize ventilator-associated lung injury
(see Chaps. 51, 52, and 55).
triggered by a large number of exogenous and endogenous molecules.
Metabolic acidosis may also decrease left ventricular contractility, but
For example, bacterial endotoxins or endogenous damage-associated its effects are less marked. Arterial blood gas measurement identifies
molecules released during ischemia-reperfusion (heat shock proteins,
metabolic acidosis in the extracellular compartment. The intracellular
compartment is affected to the extent that the metabolic acid anion
permeates the cell. Common organic acids such as lactic acid and
TABLE 35-2 Acute Reversible Contributors to Decreased Contractility ketoacids have anions that do not easily cross into the intracellular com-
Ischemia partment, so a severe metabolic acidosis may not be associated with sig-
nificant intracellular acidosis and therefore may not depress ventricular
Hypoxia contractility much. For example, lactic acidosis at a normal P begins to
CO 2
Respiratory acidosis depress contractility at pH 7.1 to 7.2, but even at a pH of 7.0 the depres-
Metabolic acidosis sion in contractility remains quite small. 38
Hypocalcemia Ionized Hypocalcemia During septic shock and in patients critically ill from
diverse causes, serum ionized calcium levels are often low. Further acute
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Hypophosphatemia
reductions may result in a substantial decrease in left ventricular con-
2+
+
Possibly other electrolyte abnormalities (Mg , K ) tractility. Decreased extracellular ionized calcium concentration results
Exogenous substances (alcohol, β-blockers, calcium channel blockers, antiarrhythmics) in decreased calcium flux during systole and decreased contractility.
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Endogenous substances (endotoxin, histamine, tumor necrosis factor, interleukin 1, After transfusion of red blood cells stored in standard citrated media,
platelet-activating factor) serum ionized calcium levels can decrease dramatically because calcium
is bound by citrate. During shock and other conditions, lactic acid, like
Hypo- and hyperthermia
citric acid, also appears to bind ionized calcium. Bicarbonate infusion
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