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To evaluate the short- and long-term effects of beta-adrenergic blockade (metoprolol) as well as the reaction to withdrawal and readministration of metoprolol in severe heart failure, 33 patients (25 men and eight women; mean age, 47.6 +/- 14.0 years) with dilated cardiomyopathy were studied by right and left heart catheterization, right ventricular biopsy, two-dimensional and Doppler echocardiography, and external pulse recordings. Twenty-six of 33 patients survived more than 6 months, and 24 of the 26 patients improved their functional class (from mean 3.3 to 1.8, p less than 0.0001). These 24 patients were subjected to withdrawal of metoprolol until the number of symptoms increased and deterioration occurred as observed noninvasively (group 1, n = 16), whereas the eight patients did not deteriorate during a 12-month period (group 2). During long-term treatment with metoprolol, there was an increase in ejection fraction from 0.24 to 0.42 (p less than 0.0001), whereas there was a decrease in the left ventricular (LV) end-diastolic dimension (from 7.3 to 6.4 cm, p less than 0.0001), in the grade of mitral regurgitation (from 1.7 to 0.4, p less than 0.0001), and in the grade of tricuspid regurgitation (from 0.6 to 0.05, p less than 0.007). There was a decrease in pulmonary wedge pressure (from 23.8 to 10.7 mm Hg, p less than 0.0001), LV end-diastolic pressure (from 24.1 to 13.4 mm Hg, p less than 0.002), and systolic vascular resistance (from 1,782 to 1,499 dynes/sec/cm, p less than 0.04). There was an increase in systolic blood pressure (from 116 to 132 mm Hg, p less than 0.003), cardiac index (from 2.17 to 2.58 l/min/m2, p less than 0.005), and LV stroke work index (from 31 to 65 g.m/m2, p less than 0.0001). During withdrawal of metoprolol, the heart rate and left atrial dimension increased (p less than 0.0001), whereas ejection fraction decreased (p less than 0.0001). The 12 (of 16) patients in group 1 who survived the withdrawal period had metoprolol readministered, and subsequently, ejection fraction increased (from 0.23 to 0.33, p less than 0.002). Patients had a low number of ventricular beta-adrenergic receptors compared with healthy control subjects (30.3 +/- 2.9 vs. 97.4 +/- 8.7 fmol/mg protein, p less than 0.001), but long-term treatment with metoprolol caused a moderate up-regulation (from 30.3 +/- 2.9 to 49.0 +/- 7.1 fmol/mg protein, p less than 0.05), which may facilitate a more normal response to sympathetic stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

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FOLKOW, B., 0. LUNDGREN and I. WALLENTIN. Studies on the relationship between Jow resistance, capillary jiltration coefjicient and regional blood volume in the intestine of the cat. Acta physiol. scand. 1963. 57. 270-283. -The relation between flow resistance, regional blood volume and capillary filtration coefficient (CFC) in the cat's intestine has been quantitatively studied at different levels of vascular smooth muscle activity, and compared to the vascular bed of the skeletal muscles. The resistance vessels of booth these vascular circuits maintain a considerable 'basal tone', but the intestine is far richer vascularized, which is obvious from the figures given for flow resistance,regional blood volume and CFC a t comparable levels of vascular tone, including maximal vasodilatation. Intestinal CFC is both in absolute and relative terms higher than in the skeletal muscles, as reflected by a definitely larger CFC/blood flow ratio over the entire range of vascular tonc. CFC thus increases considerably when vascular tone is reduced and reaches very high figures at maximal vasodilatation. This is thought to reflect an opening up of additional capillaries due to relaxation of their 'precapillary sphincters'. Reasons arc given for the belief that the glandular mucosal portion is far better vascularized than the smooth muscle portion of the intestine and at maximal vasodilatation CFC of the mucosal portion may be of the order of 1 ml/min Hg/mm/100 g of tissue. Such a figure is in fact comparable to the renal glomerular filtration, when expressed in the same wav.For several years the different 'parallel-coupled' circuits of the systemic vascular bed have been studied from a quantitative point of view in this laboratory. Obviously these circuits a r c designed to suit the need of their particular tissues a n d c a n for such reasons b e expected to show considerable differences 2 70