In dogs with asymptomatic left ventricular dysfunction, exogenous DOCA significantly increased left ventricular collagen area fraction compared to control (3.3% vs 2.0%; P=0.012).
Does mineralocorticoid excess with DOCA cause sodium/water retention and promote renal and cardiac collagen deposition in experimental asymptomatic left ventricular dysfunction?
In experimental asymptomatic left ventricular dysfunction, the kidney can escape the sodium-retaining effects of mineralocorticoid excess, but the heart suffers increased collagen deposition.
Absolute Event Rate: 3.3% vs 2%
p-value: p=0.012
Unlike healthy subjects, overt congestive heart failure cannot "escape" the sodium- and water-retaining actions of mineralocorticoid excess. It is undefined whether escape occurs in asymptomatic left ventricular dysfunction (ALVD), which is characterized by preserved sodium homeostasis, natriuretic peptide activation, and normal circulating aldosterone. We hypothesized that, in ALVD, mineralocorticoid excess with exogenous deoxycorticosterone acetate (DOCA) would overwhelm renal compensatory mechanisms, resulting in sodium and water retention, and promote renal and cardiac collagen deposition. ALVD was induced in 2 groups (N=5 each) of dogs by tachypacing at 180 bpm. Urine was collected daily and blood drawn at baseline and days 2, 5, 8, and 11. One group served as control (ALVD), and the other received DOCA (ALVD+DOCA) starting at day 2 of pacing. Urine flow and sodium excretion were unchanged in the ALVD group. In ALVD+DOCA, urine flow and sodium excretion decreased on the first 2 days DOCA was given but normalized starting day 4. Urine flow and urinary cGMP excretion increased in ALVD+DOCA after DOCA escape. Plasma atrial natriuretic peptide, B-type natriuretic peptide, and cGMP increased equally in both groups. There were no differences in cardiorenal and hemodynamic parameters in an acute study on day 11. Although renal collagen area fraction was similar, left ventricular collagen area fraction in ALVD+DOCA was significantly higher than in ALVD (3.3+/-0.4% versus 2.0+/-0.2%; P=0.012). We conclude that ALVD can escape the sodium- and water-retaining effects of mineralocorticoid excess. Despite renal escape, increased left ventricular collagen deposition suggests that the heart but not the kidney failed to escape the tissue effects of DOCA.
Costello‐Boerrigter et al. (Tue,) conducted a other in Asymptomatic left ventricular dysfunction (ALVD) (n=10). Deoxycorticosterone acetate (DOCA) vs. Control (ALVD alone) was evaluated on Left ventricular collagen area fraction (p=0.012). In dogs with asymptomatic left ventricular dysfunction, exogenous DOCA significantly increased left ventricular collagen area fraction compared to control (3.3% vs 2.0%; P=0.012).