A Review of Why and How We May Use β-Blockers in Congestive Heart Failure: Upregulation and Downregulation of β-Receptors
The normal heart has about 80% β1 and 20% β2-receptors. In CHF, it is not surprising that there are about 60% &beta:-receptors and 40% &beta:2-receptors, because theβ2-receptor response is relatively unchanged. However, by β2-stimulation tests in heart failure, there may also be a 30% decrease in their responsiveness. Therefore some downregulation may occur even with β2-receptors. However, metoprolol may also counteract β2-downregulation because it has been shown to cause an increase in β-responsiveness β-Receptor upregulation may not be the most important mechanism for the effect of β-blockers because the time course or degree of clinical improvement does not correlate with the degree of upregulation. Also, with carvedilol, a p-blocker with vasodilator and atypical p-agonist properties, there was an increase in the ejection fraction of about 10% with no increase in β-receptor density. However, metoprolol in a similar group of patients caused an increase in P-receptor density.
Antiarrkijtkmic Properties of the β-Blockers
Since nearly one half of mortality in patients with chronic DCM is due to sudden death and presumably ventricular fibrillation, P-blockers should help by their well-known ability to increase fibrillation threshold. buy asthma inhalers online
β-Blockers may prevent microentry, which is necessary for ventricular fibrillation but not macroreentry, which results in premature ventricular contractions and some ventricular tachycardias. In patients with CHF, &beta:-blockers have little effect on PVCs or short runs of ventricular tachycardia. In the β-Blocker Heart Attack Trial, patients with both arrhythmias and CHF lived longer despite no diminution of episodes of ventricular tachycardia.
Lessons To Be Learned From Negative Studies
In the negative study of Ikram and Fitzpatrick, they used acebutolol, which has intrinsic sympathomimetic activity. It is possible that the β-blocking effect on upregulation was counteracted by the sympathomimetic stimulation. Also, 12 of their 17 patients had alcohol contributing to their cardiomyopathy. Perhaps &beta:-blockade has less favorable effects on such patients.