Myocardial contractility

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

The adrenergic drugs are useful in improving hemodynamic status by improving myocardial contractility and increasing heart rate, which results in increased cardiac output. Peripheral resistance is increased by vasoconstriction. In cardiogenic shock or advanced shock associated with low cardiac output, die adrener-... 

Abnormalities of myocardial contractile and structural proteins P-Myosin heavy chains, troponin, tropomyosin, dystrophin... 

Intravenous or oral doses of a P-blocker should be administered early in the care of a patient with STE ACS, and then oral agents should be continued indefinitely. Early administration of a P-blocker to patients lacking a contraindication within the first 24 hours of hospitalization is a quality care indicator.2,3 In ACS the benefit of P-blockers mainly results from the competitive blockade of P,-adrenergic receptors located on the myocardium. Pi-Blockade produces a reduction in heart rate, myocardial contractility, and blood pressure, decreasing myocardial oxygen demand. As a result of these effects, P-blockers reduce the risk for recurrent ischemia, increase in infarct size and risk of reinfarction, and occurrence of ventricular arrhythmias in the hours and days following MI.39... 

Practitioners must have a good understanding of cardiovascular physiology to diagnose, treat, and monitor circulatory problems in critically ill patients. Eugene Braunwald, a renowned cardiologist, described the interrelationships between the major hemodynamic variables (Fig. 10-1).1 These variables include arterial blood pressure, cardiac output (CO), systemic vascular resistance (SVR), heart rate (HR), stroke volume (SV), left ventricular size, afterload, myocardial contractility, and preload. While an oversim-... 

Myeloproliferative disorder A group of diseases of the bone marrow in which excess cells, usually lymphocytes, are produced. Myelosuppression A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. Myocardial contractility The force of contraction of the heart during systole. 

Ca++-channel blockers. Verapamil has powerful effects on the heart, decreasing heart rate and myocardial contractility ( l CO) and causing some vasodilation. On the other hand, nifedipine is a more potent vasodilator (1 TPR) with weaker myocardial effects. The effects of diltiazem are somewhat intermediate, in that this drug has moderate inhibitory effects on the myocardium and vascular smooth muscle. 

Phospholamban (PLB or PLN) is a single-pass, 52-residue integral membrane protein that regulates myocardial contractility by direct physical interaction with sarco(endo)plasmic reticulum Ca-ATPase (SERCA), a 110-kDa enzyme that maintains calcium homeostasis in the sarcoplasmic... 

The benefits result from blockade of //j receptors in the myocardium, which reduces heart rate, myocardial contractility, and BP, thereby decreasing myocardial oxygen demand. The reduced heart rate increases diastolic time, thus improving ventricular filling and coronary artery perfusion. 

Acidosis occurs during cardiac arrest because of decreased blood flow and inadequate ventilation. Chest compressions generate only about 20% to 30% of normal cardiac output, leading to inadequate organ perfusion, tissue hypoxia, and metabolic acidosis. Furthermore, the lack of ventilation causes retention of carbon dioxide, leading to respiratory acidosis. The combined acidosis reduces myocardial contractility and may cause arrhythmias because of a lower fibrillation threshold. 

Heart failure (HF) is a clinical syndrome caused by the inability of the heart to pump sufficient blood to meet the metabolic needs of the body. HF can result from any disorder that reduces ventricular filling (diastolic dysfunction) and/or myocardial contractility (systolic dysfunction). 

Direct actions include vasodilation of systemic arterioles and coronary arteries, leading to a reduction of arterial pressure and coronary vascular resistance as well as depression of myocardial contractility and the conduc-... 

Edema can occur in patients with decreased myocardial contractility, nephrotic syndrome, or cirrhosis. 

Cardiovascular manifestations result in ECG changes characterized by a prolonged QT interval and symptoms of decreased myocardial contractility often associated with heart failure. 

Luo W, Grupp IL, Harrer J et al 1994 Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation. Cite Res 75 401 —409... 

Cardiovascular effects Harmala alkaloids have cardiovascular effects (Aarons et al. 1977). Harmine, harmaline, and harmalol decrease heart rate, but increase pulse pressure, peak aortic flow, and myocardial contractile force in dogs. Harmine reduces systemic arterial blood pressure and peripheral vascular resistance. Vascular resistance effects are not mediated by jS-adrenergic or histamine HI receptors. 

Most members of the imidazolylphenylpyridazinone series have been found to produce dose-related increases in myocardial contractility that were associated with minor increases in heart rate and decreases in systemic arterial blood pressure. Studies of structure-activity relationships in this class have been published [25-27]. 

Calcium-channel blockers interfere with the inward movement of calcium ions through the cell membrane channels. This results in reduction of myocardial contractility (hence negative inotropes), reduction of cardiac output and arteriolar vasodilatation. The dihydropyridine group, such as nifedipine and amlodipine, which may be used in the management of hypertension, are very effective as arterial vasodilators, whereas diltiazem and verapamil are very effective in reducing atrioventricular conduction. 

Due to their cationic amphiphilic nature, the TCA exert membrane-stabilizing effects that can lead to disturbances of cardiac impulse conduction with arrhythmias as well as decreases in myocardial contractility. All TCA lower the seizure threshold. Weight gain may result from a stimulant effect on appetite. 

Secondary hypotension is a sign of an underlying disease that should be treated first. If stroke volume is too low, as in heart failure, a cardiac glycoside can be given to increase myocardial contractility and stroke volume. When stroke volume is decreased due to insufficient blood volume, plasma substitutes will be helpful in treating blood loss, whereas aldosterone deficiency requires administration of a mineralocor-ticoid (e.g., fludrocortisone). The latter is the drug of choice for orthostatic hypotension due to autonomic failure. A parasympatholytic (or electrical pacemaker) can restore cardiac rate in bradycardia. 

Several studies have indicated that n-butane sensitizes the myocardium to epinephrine-induced cardiac arrhythmias. In anesthetized dogs, 5000 ppm caused hemodynamic changes such as decreases in cardiac output, left ventricular pressure, and stroke volume, myocardial contractility, and aortic pressure. Exposure of dogs to 1-20% butane for periods of 2 minutes to 2 hours hypersen-... 

Inhalation studies with chloropentafluoroethane in anesthetized dogs, rats, and monkeys showed that exposure to 100,000-2 5 0,000 ppm, under certain conditions, caused an increase in blood pressure, accelerated heart rate, depression of myocardial contractility and sensitized the heart to epinephrine.Compared with other chlorofluorocarbons, it is ranked among the least potent for cardiac sensitization." ... 

Propranolol is a prototype of this series of drugs and is the oldest and most widely used nonselective )3-adrenoblocker. It possesses antianginal, hypotensive, and antiarrhythmic action. Propranolol is a cardiac depressant that acts on the mechanic and electrophysio-logical properties of the myocardium. It can block atrioventricular conductivity and potential automatism of sinus nodes as well as adrenergic stimulation caused by catecholamines nevertheless, it lowers myocardial contractility, heart rate, blood pressure, and the myocardial requirement of oxygen. 

Use quinidine with extreme caution in incomplete AV block, because complete block and asystole may result. The drug may cause unpredictable dysrhythmias in digitalized patients. Use cautiously in patients with partial bundle branch block, severe CHF, and hypotensive states due to the depressant effects of quinidine on myocardial contractility and arterial pressure. 

CHF Use with caution in patients with CHF and in those with acute ischemic heart disease or cardiomyopathy because even slight depression of myocardial contractility may further reduce cardiac output of the damaged heart. 

Verapamil IV- Do not administer concomitantly with IV -adrenergic blocking agents (within a few hours), because both may depress myocardial contractility and AV conduction ventricular tachycardia (VT), because use in patients with wide-complex VT (QRS 0.12 seconds or more) can result in marked hemodynamic deterioration and ventricular fibrillation atrial fibrillation or atrial flutter associated with an accessory bypass tract. 

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