Adrenomedullin: view on a novel vasodilatory peptide with natriuretic properties.

Although initially described in human pheochromocytoma, adrenomedullin has been isolated in several animal and human peripheral organs, including cardiovascular tissues. In experimental models, adrenomedullin exerts potent vasodilatory and natriuretic properties which could participate to maintain physiological cardiovascular and renal homeostasis. Whether adrenomedullin is powerful in humans remains to be proven. On the basis of increased plasma levels in hypertension and heart failure, adrenomedullin is suspected to contribute to the pathogenesis of these diseases. A reduced clearance is another possibility but has not yet been investigated in these pathological states. Finally, the ubiquitous distribution of adrenomedullin suggest various other biological activities that need to be established in future

Endothelin-1 receptor antagonism does not influence myocardial function in hypertensive dogs.

BACKGROUND: As endothelin-1 exerts positive inotropic effects, the present study evaluated whether the hypotensive effects of the endothelin-1 receptor antagonist bosentan were partially related to a decrease in myocardial performance. METHODS: In group I, eight anaesthetized open-chest dogs with perinephritic hypertension received four cumulative doses of bosentan (B1-B4). In group II, eight animals received the same doses of bosentan after autonomic blockade. Indices of heart function were derived from the pressure-length loops obtained during vena cava occlusion. RESULTS: In group I, bosentan decreased left ventricular systolic pressure (LVSP) and mean aortic pressure (MAP) dose dependently, reaching 21% and 23% respectively at B4 (LVSP from 190 +/- 8 to 150 +/- 5 mmHg, P < 0.001; MAP from 167 +/- 7 to 128 +/- 5 mmHg, P < 0.001). These effects were only related to peripheral vasodilatation, without depression of myocardial contractility, as systemic vascular resistance dropped (from 670 +/- 83 to 446 +/- 53 mmHg mL-1 min-1 x 10(4); P < 0.05), and the end-systolic pressure-length relationship (ESPLR) remained unchanged (4.0 +/- 0.4 vs. 4.3 +/- 0.7 mmHg mm-1 kg-1). Concomitantly with pressure decline, heart rate tended to increase in this group (from 150 +/- 4 to 156 +/- 6 beats min-1). When autonomic system was blocked (group II), administration of bosentan induced similar hypotensive effects as in group I (26% and 28% reduction in LVSP and MAP respectively, P < 0.001) whereas ESPLR did not change (3.0 +/- 0.9 vs. 3.1 +/- 0.5mmHg-1 mm kg-1 ). Under these sympathetically blocked conditions, heart rate significantly fell after bosentan infusion (from 120 +/- 4 to 110 +/- 6 beats min-1, P < 0.001). CONCLUSIONS: Without influencing heart function, bosentan is an efficient and safe therapy that opens up new therapeutic perspectives in human essential hypertension

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Pressure-derived fractional flow reserve to assess serial epicardial stenoses : theoretical basis and animal validation

Background: Fractional flow reserve (FFR) is an index of stenosis severity validated for isolated stenoses. This study develops the theoretical basis and experimentally validates equations for predicting FFR of sequential stenoses separately. Methods and Results: For 2 stenoses in series, equations were derived to predict FFR (FFRpred) of each stenosis separately (ie, as if the other one were removed) from arterial pressure (Pa), pressure between the 2 stenoses (Pm), distal coronary pressure (Pd), and coronary occlusive pressure (Pw). In 5 dogs with 2 stenoses of varying severity in the left circumflex coronary artery, FFRpred was compared with FFRapp (ratio of the pressure just distal to that just proximal to each stenoses) and to FFRtrue (ratio of the pressures distal to proximal to each stenosis but after removal of the other one) in case of fixed distal and varying proximal stenoses (n=15) and in case of fixed proximal and varying distal stenoses (n=20). The overestimation of FFRtrue by FFRapp was larger than that of FFRtrue by FFRpred (0.070±0.007 versus 0.029±0.004,

Pressure-derived fractional flow reserve to assess serial epicardial stenoses : theoretical basis and animal validation

Background: Fractional flow reserve (FFR) is an index of stenosis severity validated for isolated stenoses. This study develops the theoretical basis and experimentally validates equations for predicting FFR of sequential stenoses separately. Methods and Results: For 2 stenoses in series, equations were derived to predict FFR (FFRpred) of each stenosis separately (ie, as if the other one were removed) from arterial pressure (Pa), pressure between the 2 stenoses (Pm), distal coronary pressure (Pd), and coronary occlusive pressure (Pw). In 5 dogs with 2 stenoses of varying severity in the left circumflex coronary artery, FFRpred was compared with FFRapp (ratio of the pressure just distal to that just proximal to each stenoses) and to FFRtrue (ratio of the pressures distal to proximal to each stenosis but after removal of the other one) in case of fixed distal and varying proximal stenoses (n=15) and in case of fixed proximal and varying distal stenoses (n=20). The overestimation of FFRtrue by FFRapp was larger than that of FFRtrue by FFRpred (0.070±0.007 versus 0.029±0.004,