Heart contractility

The hemodynamic effects of compounds supposed to affect the cardiovascular system are evaluated by measuring preload and afterload of the heart, contractility, heart rate, cardiac output and peripheral or coronary flow. To measure these cardiovascular parameters accurately, the use of larger animals such as dogs or pigs is necessary. This experimental model allows the classification of test drugs according to their action as having ... 

Pj-selective agonists such as prenalterol (Figure 10.5) or dobutamine are used to stimulate heart contractility and heart rate in patients that exhibit too low blood pressure. P2-Selective agents such as terbutaline find application for relaxation and dilatation of the bronchi in the treatment of asthma or chronic obstmctive lung disease, and in the suppression of premature labour. The mechanism of P-receptor-induced relaxation of smooth muscle - cAMP-mediated phosphorylation and inhibition of myosin light chain kinase - has been described before. 

Stimulate neurotransmitter release Increase heart contractility Decrease peripheral vasocohstriction Increase carbohydrate metabolism... 

Inhibits L-type Ca " channels in cardiac and vascular smooth muscle cells by modulating ion channel gating mechanisms decreases systemic blood pressure and heart contractility... 

Inhibits L-type Ca" channels in cardiac and vascular smooth muscle cells more selective for the myocardium with minimal vasodilatory effects compared with dihydropyridines class IV antiarrhythmic agents Inhibits L-type Ca " " channels in cardiac and vascular smooth muscle cells by modulating ion channel gating mechanisms decreases systemic blood pressure and heart contractility Binds with high affinity to the alpha2-delta subunit of voltagegated Ca " " channels in CNS anticonvulsant drug Inhibits neuronal fast Nay channels, and thus blocks the action potential inhibits also cardiac Nay channels... 

Several types of action on the cardiovascular system will be dealt in here action on the heart (contractile force, automaticity, rythmicity, effect on... 

Isradipine (Dynacirc) Selectively inhibits vascular smooth muscle contraction and S-A node conduction with little effect on heart contractility or A-V node conduction. Angina, hypertension. Little tachycardia because of selective actions. Headache, peripheral edema, and flushing. 

Two earlier studies in patients and healthy subjects had found that the pharmacokinetics of flecainide and verapamil were only minimally affected by concurrent use, but the PR interval was increased by both drugs and additive depressant effects were seen on heart contractility and AV conduction. No serious adverse responses occurred. 

Seubert JM, Sinai CJ, Graves J, DeGrafif LM, Bradbury JA, Lee CR, Goralski K, Carey MA, Luria A, Newman JW, Hammock BD, Falck JR, Roberts H, Rockman HA, Murphy E, Zeldin DC (2006) Role of soluble epoxide hydrolase in postischemic recovery of heart contractile function. Cire Res 99 442-450... 

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