Abstract 4871: Vasopressin V1 Receptor Improves Left Ventricular Systolic and Diastolic Performance at Rest and During Exercise after Heart Failure
Previously, we demonstrated that in conscious animals, arginine vasopressin (AVP), a potent vasoconstrictor, directly depresses left ventricular (LV) contractility. In heart failure (HF), circulating levels of AVP are increased and are further elevated during exercise (Ex). Thus, AVP blockade may prevent Ex-induced exacerbation of LV systolic and diastolic dysfunction and improve Ex tolerance in HF. We assessed acute effects of a specific AVP V1-receptor antagonist (V1-ANT), [Pmp1,Tyr(OMe)2, Arg8] vasopressin (25–30 μg/kg, iv), on LV diastolic filling and LV-arterial coupling during Ex in 10 conscious chronically-instrumented dogs with pacing induced HF. After HF, Ex produced significant increases in LV end-systolic pressure (PES, 117 vs 106 mmHg), minimum LV pressure (P) (22.6 vs 18.8 mmHg), and the time constant of LV relaxation (τ, 39.1 vs 36.8 ms). LV filling rate (dV/dtmax, 212 vs 150 ml/s) was increased due to elevated mean left atrial (LA) P (32.7 vs 25.1 mmHg) (p<0.05) with an upward shift of early diastolic portion of LV P-V loop. During Ex, LV contractility (EES, 2.2 vs 3.6 mmHg/ml) decreased and arterial elastance (EA, 8.2 vs 7.8 mmHg/ml) increased. Thus, LV-arterial coupling, quantified as EES/EA, was further impaired. Compared with HF at rest, treatment with V1-ANT completely prevented Ex-induced increases in τ(Δτ=−2.2 vs 2.3 msec), EA (ΔEA = −0.4 vs 0.4 mmHg/ml) and minimum LV P (ΔP= 0.4 vs 3.7 mmHg). V1-ANT caused a downward shift of LV P-V loops during Ex with further augmented LV filling rate (ΔdV/dtmax = 74 vs 62 ml/sec). Moreover, compared with HF at rest, during Ex after treatment with V1-ANT, EES/EA was increased (0.56 vs 0.38) due to decreased EA (7.4 vs 7.9 mmHg/ml) and increased EES (4.3 vs 3.6 mmHg/ml). LV mechanical efficiency, the ratio of stroke work to total P-V area (0.51 vs 0.41), was also significantly improved. After HF, V1-ANT produces arterial vasodilatation; improves LV-arterial coupling and mechanical efficiency, thus prevents Ex-induced exacerbation of LV systolic and diastolic dysfunction; and improves Ex tolerance with HF.