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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of regional alpha- and beta-blockade on resting and hyperemic coronary blood flow in conscious, unstressed humans.

Our purpose was to determine if there are basal adrenergic influences on the coronary circulation in humans. We studied 56 patients with denervated hearts after cardiac transplantation and 19 normally innervated patients with angiographically normal coronary arteries. Coronary blood flow velocity was measured during cardiac catheterization with a subselective 3F intracoronary Doppler catheter. Heart rate was controlled by atrial pacing. Epicardial coronary artery diameter was measured by automated analysis of digital coronary angiograms. Coronary flow reserve was assessed by intracoronary papaverine hydrochloride (12 mg) injections. Regional sympathetic blockade was produced by intracoronary injections of phentolamine (3 mg, alpha) and propranolol (2 mg, beta) or metoprolol (3 mg, beta 1). After alpha-blockade, mean arterial pressure fell significantly (p less than 0.05) in both the denervated transplant (-5.8 +/- 1.5%) (mean +/- SEM) and normally innervated patients (-12.6 +/- 3.2%). Reductions in coronary flow velocity also were observed in these groups (-8.2 +/- 2.3% and -9.2 +/- 5.8%, respectively). Calculated coronary vascular resistance was unchanged. Similar changes were seen when patients were pretreated with beta-blockade before alpha-blockade. Nonspecific beta-blockade did not affect mean arterial pressure but decreased coronary velocity (innervated, -11.6 +/- 3.9%; denervated, -9.3 +/- 2.4%) and increased coronary vascular resistance (innervated, 15.4 +/- 6.7%; denervated, 10.2 +/- 3.7%). Coronary vascular resistance did not rise in either group after selective beta 1-blockade with metoprolol. Coronary flow reserve did not change in either patient group after either alpha- or beta-blockade. Changes in epicardial coronary artery diameter were small and generally not significant. These data suggest that alpha-receptor-mediated vascular tone is negligible in both denervated transplant patients and normally innervated patients. Additionally, the increase in vascular resistance after nonselective beta-blockade is the result of direct beta 2 vascular effects. Our data further suggest that there is little adrenergically mediated epicardial artery tone (either humoral or neural) at rest and that maximal vasodilator responses are not limited by adrenergically mediated vasomotor tone.[1]


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