Negative chronotropic properties

Verapamil and diltiazem cause less peripheral vasodilation than dihydro-pyridines such as nifedipine but greater decreases in AV node conduction. They must be used with caution in patients with preexisting conduction abnormalities or in patients taking other drugs with negative chronotropic properties. 

P-blocker therapy was ineffective in preventing coronary heart disease, cardiovascular mortality, and all-cause mortality when compared to diuretics for elderly patients (60 years of age or greater) treated for primary hypertension. Clearly, the effects of P-blockers on blood pressure are complex and difficult to ascribe to one or two mechanisms. Rather, the varied effects of negative chronotropic and inotropic properties along with reduced renin levels (Fig. 2-3) appear to result in an overall reduction in cardiac output and/or reduction in peripheral resistance. 

Beta blockers bind to beta-1 receptors on the myocardium and block the effects of norepinephrine and epinephrine (see Chapter 20). These drugs therefore normalize sympathetic stimulation of the heart and help reduce heart rate (negative chronotropic effect) and myocardial contraction force (negative inotropic effect). Beta blockers may also prevent angina by stabilizing cardiac workload, and they may prevent certain arrhythmias by stabilizing heart rate.40 These additional properties can be useful to patients with heart failure who also have other cardiac symptoms. 

In man berberine has positive inotropic, negative chronotropic, antidysrhythmic, and vasodilator properties (1) and there is experimental evidence that it can cause arterial hypotension (2,3). 

The toxic effects of propranolol are related to its negative inotropic and chronotropic properties, which can lead to sinus bradycardia and hypotension. These complications should be treated with an acute inotrope such as dopamine or dobutamine. 

Nicardipine has antianginal properties similar to those of nifedipine and may have selectivity for coronary vessels. Isradipine also produces the typical peripheral vasodilation seen with other dihydropyridines, but because of its inhibitory effect on the sinoatrial (SA) node, little or no rise in heart rate is seen. This inhibitory effect does not extend to the cardiac myocytes, however, because no cardiodepres-sant effect is seen. Despite the negative chronotropic effect, isradipine appears to have little effect on the atrioventri-cnlar (AV) node, so it may be used in patients with AV block or combined with a P-adrenergic-receptor antagonist. 

In a study using isolated guinea pig hearts, phthalide 20 exhibited negative chronotropic and inotropic responses and attenuated the decrease in coronary flow induced by pituitrin. This demonstrated the preload- and afterload-reducing properties of 20, which may contribute to its anti-anginal effect in vivo [305], This speculation, however, was challenged by the results in that 20 decreased the heart rate in renal hypertensive anesthetized rats [302] but its Z-isomer 22 did not affect the heart rate in normotensive conscious rats [303]. The impacts of phthalides 20 and 22 on cardiac function and angina pectoris/myocardial ischemia remain uncertain. 

Berberine has been used in the treatment of several heart diseases including hypertension and arrhythmia in folk medicine [46, 47]. Several pharmacological studies have shown the beneficial effects of berberine oti diverse cardiovascular disorders in animal and human, including prevention of ischemia-induced ventricular tachyarrhythmia, improvement of cardiac contractile function, and reductirMi of peripheral vascular resistance and blood pressure [48, 49]. Berberine has also positive inotropic, negative chronotropic, antiarrhythmic, vasodilator, and antiatherosclerosis properties [50]. 

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