Cardiovascular effects of berberine in patients with severe congestive heart failure

Berberine, an alkaloid of the protoberberine family, has been shown to have strong positive inotropic and peripheral resistance-lowering effects in dogs with and without heart failure. To determine the acute cardiovascular effects of berberine in humans, 12 patients with refractory congestive heart failure were studied before and during berberine intravenous infusion at rates of 0.02 and 0.2 mg/kg per min for 30 minutes. The lower infusion dose produced no significant circulatory changes, apart from a reduction in heart rate (14%). The 0.2 mg/kg per min dose elicited several significant changes: (a) Decreases in systemic (48%, p>0.01) and pulmonary vascular resistance (41%, p>0.01), and in right atrium (28%, p>0.05) and left ventricular end-diastolic pressures (32%, p>0.01). (b) Increases in cardiac index (45%, p>0.01), stroke index (45%, p>0.01), and LV ejection fraction measured by contrast angiography (56%, p>0.01). (c) Increases in hemodynamic and echocardiographic indices of LV performance: peak measured velocity of shorten: ing (45%, p>0.01), peak shortening velocity at zero load (41%, p>0.01), rate of development of pressure at developed isovolumic pressure of 40 mmHg (20%, p>0.01), percent fractional shortening (50%, p>0.01), and the mean velocity of circumferential fiber shortening (54%, p>0.01). (d) Decrease of arteriovenous oxygen difference (28%, p>0.05) with no changes in total body oxygen uptake, arterial oxygen tension, or hemoglobin dissociation properties. These salutary acute effects show that berberine markedly improved cardiac performance in patients with heart failure refractory to conventional medical therapy with digitalis and diuretics. The improvement is probably subsequent to peripheral vasodilatation and to inotropic stimulation. Significant untoward effects appear to be the development of ventricular tachycardia with “torsades de pointes” morphology, detected in 4 patients 1-20 h after the infusion of berberine. This possible association requires further elucidation before the administration of berberine may be extended to other patients in heart failure.