Beneficial hemodynamic and renal effects of adrenomedullin in an ovine model of heart failure.

BACKGROUND: Adrenomedullin is a recently discovered endogenous peptide with hypotensive and natriuretic actions in normal animals. Circulating and ventricular adrenomedullin are elevated in congestive heart failure, suggesting a possible role in the pathophysiology of this disease. No studies have previously examined the effects of adrenomedullin in heart failure. METHODS AND RESULTS: Eight sheep with pacing-induced heart failure received human adrenomedullin(1-52) at 10 and 100 ng x kg(-1) x min(-1) I.V. for 90 minutes each. Compared with vehicle control data, adrenomedullin increased plasma cAMP (high dose, P<.05) in association with dose-dependent falls in calculated peripheral resistance (13 mm Hg x L(-1) x min(-1), P<.001), mean arterial pressure (9 mm Hg, P<.001), and left atrial pressure (5 mm Hg, P<.001) and increases in cardiac output (0.5 L/min, P<.001). Adrenomedullin increased urine sodium (threefold, P<.05), creatinine (P<.05) and cAMP excretion (P<.01), creatinine clearance (P<.05), and renal production of cAMP (P<.05), whereas urine output was maintained during infusion and raised after infusion (P<.05). Adrenomedullin reduced plasma aldosterone levels (P<.05), whereas plasma atrial and brain natriuretic peptide concentrations were unchanged during infusion and rose after infusion (P<.01 and P<.05, respectively). Plasma catecholamine, cortisol, renin, calcium, and glucose concentrations were not significantly altered. CONCLUSIONS: Adrenomedullin reduced ventricular preload and afterload and improved cardiac output in sheep with congestive heart failure. Despite the clear fall in arterial pressure, adrenomedullin increased creatinine clearance and sodium excretion and maintained urine output. These results imply an important pathophysiological role for adrenomedullin in the regulation of pressure and volume in heart failure and raise the possibility of a new therapeutic approach to this disease.

Overcoming perioperative spasm of the internal mammary artery: which is the best vasodilator?

After mobilization, vasospasm often reduces flow through the internal mammary artery. An established method of relaxing the artery and increasing flow is to wrap it in a papaverine-soaked swab. To our knowledge the ability of other topical vasodilators to overcome spasm of the internal mammary artery has not been studied clinically. In 50 patients in whom the left mammary artery was used for myocardial revascularization, we have investigated the effect of five agents on internal mammary artery free flow. The agents investigated were normal saline, papaverine, nifedipine, glyceryl trinitrate, and sodium nitroprusside. Under controlled hemodynamic conditions, free flow was measured before any pharmacologic intervention and a median of 18.5 minutes after the pedicle had been sprayed with one of the five agents. Normal saline produced a small increase in flow from a median of 23 ml/min (range 17 to 88) to 38 ml/min (20 to 84) (not significant), whereas a significant increase occurred with papaverine, from 25 (16 to 78) to 43 ml/min (34 to 112) (p less than 0.01). Nifedipine and glyceryl trinitrate raised free flow by almost threefold, from 23 (14 to 66) to 71 ml/min (45 to 118) and from 23 (14 to 58) to 62 ml/min (46 to 126), respectively (both p less than 0.001). Sodium nitroprusside, however, with an increase in flow from 26 (10 to 58) to 108 ml/min (46 to 196), 250% over control, proved to be more effective than nifedipine and glyceryl trinitrate (p less than 0.05). We therefore recommend the topical use of sodium nitroprusside to relieve perioperative spasm of the internal mammary artery.

Iodide excretion in a salt-restriction trial.

Twenty-four hour urinary iodide excretion was measured twice, with a four month interval, in 133 individuals who were in a 12-month salt-restriction study in an area where iodine-deficiency goitre was once common and where most household salt is iodised. Half the subjects were salt restricted; their mean 24 h sodium excretion after eight months was 89 mmol for men and 73 mmol for women. Iodide excretion correlated with sodium excretion in the whole group on each occasion. After eight months mean 24 h iodide excretion in the salt-restricted group (men 1.3 SD 0.6 mumol, women 1.1 SD 0.4 mumol) was lower (p less than 0.01) than that in the control group (men 1.8 SD 0.8 mumol, women 1.7 SD 0.8 mumol), but was reasonable in terms of recommended dietary allowances (1.2 mumol, 150 mg). Mean iodide content of local milk was 1.3 mumol/l. Any salt that is used in the home should continue to be iodised. However, it has become unnecessary in this population to use salt (ie, iodised salt) simply in order to avoid iodine deficiency, so long as other foodstuffs continue to contain iodine as at present. As the other sources of iodine may be subject to change, the adequacy of intake of iodine from these sources should be monitored from time to time in samples of the population.