Background The aortic root enlarges progressively in Marfan's syndrome, and this enlargement is associated with aortic regurgitation and dissection. Long-term treatment with β-adrenergic blockade, by reducing the impulse (i.e., the rate of pressure change in the aortic root) of left ventricular ejection and the heart rate, may protect the aortic root. Methods We conducted an open-label, randomized trial of propranolol in adolescent and adult patients with classic Marfan's syndrome (32 treated and 38 untreated [control] patients). Aortic-root dimensions and clinical end points (aortic regurgitation, aortic dissection, cardiovascular surgery, congestive heart failure, and death) were monitored for an average of 9.3 years in the control group and 10.7 years in the treatment group. All 70 patients were included in the analysis according to the intention-to-treat principle. Results The dose of propranolol was individualized; the mean (±SE) dose was 212 ±68 mg per day. The mean slope of the regression line for ...

https://www.nejm.org/doi/pdf/10.1056/NEJM199405123301902

Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome

"The present results indicate that there is a close relationship between the incretory function of the kidney, which is shown by the discharge of renin and similar materials, and the function of the adrenal cortex, especially the zona glomerulosa, which is the place of production of the sodium-retaining hormone aldosterone . Salt load inhibits the production of renin and aldosterone, while salt deprivation stimulates the production of both. The excess of sodium-retaining corticoids (DOC or aldosterone) together with sodium suppress the secretion of renin, while a deficiency of cortical hormones (adrenalectomy, morbus Addison) increase it." ... "Under these conditions the development of experimental renal hypertension could be explained as follows: the narrowing of the renal artery stimulates the secretion of renin which itself increases the formation or discharge of mineralocorticoid hormones (aldosterone or similarly acting corticoids). The resulting retention of sodium does not lead to the normal reduction of renin secretion in the ischemic kidney, so that corticoid production in the adrenal cortex is further stimulated despite no need for it."

The renin-angiotensin-aldosterone system. Past, present and future.

Angiotensins are peptide hormones derived from the protein precursor angiotensinogen by the sequential actions of proteolytic enzymes (Figure 1). The classic pathway of angiotensin synthesis includes a reaction catalyzed by angiotensin-converting enzyme (ACE), which occurs not only in plasma but also in the kidneys, brain, adrenal glands, ovaries, and possibly other tissues.1 The intrarenal renin–angiotensin system affects glomerular filtration, as discussed below, but the importance of angiotensin synthesis in other tissues is not known. Angiotensin II, the principal effector of the renin–angiotensin cascade, can also be synthesized by a pathway that does not require ACE.2 Angiotensin II stimulates a variety . . .

Angiotensin Receptors and Their Antagonists

Thoracic aortic aneurysm and dissection.

The clinical significance of inhibition of renal prostaglandin synthesis

It has been argued that pulse wave characteristics are important factors in extension and rupture of acute dissecting aneurysms. To test this, a standard model of an aorta was constructed, consisting of an outer layer of Tygon tubing and an inner layer of rubber cement. An "intimal tear" was produced and the "aorta" was subjected to nonpulsatile and pulsatile flow with increasing increments of pressure.

With nonpulsatile flow alone (97 experiments) no dissection occurred at pressures up to 400 mm Hg. Pulsatile flow produced rapid and usually complete dissection with a maximum systolic pressure of 120 mm Hg.

The extent of dissection per pulse was related to dp/dtmax in the fluid. No dissection occurred until a critical value of dp/dtmax (790 mm Hg/sec) was reached. Dog aortas were then used in place of the Tygon tube "aorta" with similar results; i.e., dissection did not occur with nonpulsatile flow, but did occur with pulsatile flow (3800 mm Hg/sec). The dissecting dog aorta ruptured to the outside or reentered the vessel lumen.

It was concluded that pulse wave characteristics, particularly dp/dtmax, are important in the propagation of dissection.

Edward K. Prokop

Papers

Hydrodynamic Forces in Dissecting Aneurysms In-Vitro Studies in a Tygon Model and in Dog Aortas