Myocardial contractile force

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. 

C. Nitroglycerin can increase heart rate via an increase in sympathetic tone to the heart due to an excessive decrease in blood pressure propranolol would block the p-receptors responsible for the tachycardia. Propranolol does not decrease preload, and its effect to decrease afterload would exacerbate the decrease in afterload produced by nitroglycerin. Propranolol does not increase myocardial contractile force and could actually increase the incidence of vasospasm by unmasking a-adrenocep-tors in the coronary blood vessels. 

Theophylline, given as the soluble ethylenediamine salt aminophylline, offers some help in relieving the paroxysmal dyspnea that is often associated with left heart failure. A major portion of its efficacy may be due to the relief of bronchospasm secondary to pulmonary vascular congestion. Theophylline increases myocardial contractile force and has occasionally been used in the treatment of refractory forms of congestive heart fail-... 

Epinephrine and norepinephrine produce an increase in coronary blood flow. Nevertheless, these agents have a deleterious effect on patients with angina pectoris because the increased CBF is insufficient to meet an increased oxygen requirement, which is a result of increased blood pressure, heart rate, and myocardial contractile force. 

Kahler RL, Goldblatt A and Braunmad E (1962). The effects of acte hypoxia on the systemic venous and arterial systems and on myocardial contractile force. J Clin Invest, 41, 1553-1563. 

Recent evidence points to a local release of catecholamines as the major mode of action of amantadine in parkinsonism. This is the most sensitive effect of amantadine reported to date and occurs at the lowest dose. Althou earlier clues pointed to this action, the results of Grelak et al. clarified this point. They reported that a small transient pressor effect of amantadine alone, intravenously in dogs, was markedly intensified by dopamine-priming. This suggested that amantadine released dopamine and/or other catecholamines from neuronal scores to cause Che peripheral pressor action. The effect was noted at very low amantadine doses. There was no evidence for block of dopamine uptake. Earlier Vernier reported that transient increases in myocardial contractile force occurred following moderate intravenous doses of amantadine. These also suggested local catecholamine release, since they were abolished by reserpinlzatlon and restored by norepinephrine infusion. 

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. 

The effects of phenytoin on the cardiovascular system vary with the dose, the mode and rate of administration, and any cardiovascular pathology. Rapid administration can produce transient hypotension that is the combined result of peripheral vasodilation and depression of myocardial contractility. These effects are due to direct actions of phenytoin on the vascular bed and ventricular myocardium. If large doses are given slowly, dose-related decreases in left ventricular force, rate of force development, and cardiac output can be observed, along with an increase in left ventricular end-diastolic pressure. 

Angiotensin II stimulates the influx of Ca" " into cardiac muscle cells and can exert a direct inotropic effect at cardiac muscle. In addition, angiotensin II can stimulate the sympathoadrenal system and thereby increase myocardial contractility. In contrast to its effects on vascular smooth muscle, the ability of angiotensin to increase the contractile force of the heart is far less potent. Therefore, in spite of the positive chronotropic and inotropic effects produced by angiotensin II, cardiac output is rarely increased. In fact, angiotensin II may decrease cardiac output through reflex bradycardia induced by the rise in peripheral resistance that it causes. In contrast, centrally administered angiotensin II increases both blood pressure and cardiac output. 

Treatment of myocardial malfunction and tissue damage. It is desirable to induce a slower heartbeat (bradycardia) in order to reduce O2 consumption without causing a reduction in contractile force. Existing drugs (calcium channel blockers) could also reduce the contractile force of myocardial tissue which is undesirable. 

In the past, beta blockers were considered detrimental in patients with heart failure.60 As indicated in Chapter 20, these drugs decrease heart rate and myocardial contraction force by blocking the effects of epinephrine and norepinephrine on the heart. Common sense dictated that a decrease in myocardial contractility would be counterproductive in heart failure, and beta blockers were therefore contraindicated in heart failure.60,69 It is now recognized that beta blockers are actually beneficial in people with heart failure because these drugs attenuate the excessive sympathetic activity associated with this disease.56,64 As indicated earlier,... 

The toxicity of papaverine has been studied,36 as have its effects on energy processes in myocardial mitochondria,37 on the release and metabolism of dopamine,38 on contractile force and C-nucleotide levels in dog myocardium,39 on serum-induced spasms in cerebral arterioles,40 and on production of PGE2 by rabbit gastric mucosa,41 and the biological effects of drotaverine,42 N-benzoylpapaverinium chloride,43 and norlaudanosoline44 have been studied. A rapid method for the determination of papaverine in plasma by h.p.l.c. has been described.45... 

F]Fluoroisopropyl derivatives of benzylamine and norephedrine have been prepared1 7 as shown in equation 57. 99 is of great clinical interest for PET visualization and quantification of myocardial / ,-adrenergic receptors, which are involved in the regulation of the rate and the contractile force of the myocardium. 

To better understand certain aspects of the mechanism of digitalis drugs, it would be useful to outline briefly their cardiovascular properties. The increased force of myocardial contraction produced by these glycosides is by far their most dramatic pharmacodynamic property. This positive inotropic (increased contractile force) action translates into increased cardiac output and effects on cardiac size and blood volume through diuresis (i.e., the relief of the edema that accompanies CHF). The rate of tension development is apparently affected, not the length of time during which contraction is maintained by the muscle fiber. Digitalis exerts its effect even in the presence of p-blockers or reserpine. 

Nifedipine acts primarily at the level of the vasculature, and has little effect on the myocardium. Thus, the efficiency of the heart would be increased, and the work of the heart decreased. With verapamil therapy, both cardiac conduction and contractile force would be affected, resulting in a decrease in myocardial efficiency. 

These drugs cause dilation of veins. Venodilation results in a decrease in preload, and decreased ventricular filling, which decreases the load to the myocardium and increases myocardial efficiency (i.e., by Starling s law). The decrease in preload contributes to a decreased fiber stretch, and optimal actin-myosin interaction, which results in increased contractile force and increased myocardial efficiency. 

After a study of the cardiac depressant action of KL-255, it was suggested that myocardial depression may be a result of 3-blockade of the basal tone established by endogenously released catecholamines. Catecholamine depletion by guanethidine resulted in a loss of the depression of contractile force normally observed with KL-255. The depressant effects did not appear to be dose-related to local anesthetic action. 

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