Experimental Studies AT 1 Angiotensin II Receptor Inhibition in Pacing- Induced Heart Failure: Effects on Left Ventricular Performance and Regional Blood Flow Patterns

Background: AT l angiotensin II (AT I Ang II) receptor activation has been shown to cause increased vascular resistance in the systemic (SVR), pulmonary (PVR), and coronary vasculature which may be of particular importance in the setting of congestive heart failure (CHF). The overall goal of this study was to examine the effects of acute AT 1 Ang II receptor inhibition on left ventricular (LV) pump function, systemic hemodynamics, and regional blood flow patterns in the normal state and with CHF, both at rest and with treadmill-induced exercise. Methods and Results: Pigs (25 kg) were instrumented to measure cardiac output (CO), SVR, and PVR, and LV myocardial blood flow distribution in the conscious state and were assigned to one of two groups: (1) pacing-induced CHF (240 bpm for 3 weeks, n = 6) or (2) sham controls (n = 5). Measurements were obtained at rest and after treadmill exercise (15 ° for 10 minutes). Studies were repeated 30 minutes after intravenous infusion of a low (1.1 mg/kg) or high (125 mg/kg) dose of the AT~ Ang II antagonist, valsartan. The low dose of valsartan reduced the Ang II pressor response by approximately 50% but had a minimal effect on arterial pressure, whereas the high dose eliminated the Ang II pressor response and reduced resting blood pressure by approximately 20%. With CHF, CO was reduced at rest (2.5 -+ 0.2 v 3.9 -+ 0.1 L/rain) and with exercise (6.4 _+ 0.5 v 7.8 + 0.5 L/min) compared with controls (P < .05). Valsartan at the low and high dose increased resting CO by 28% in the control and CHF groups, but did not affect CO with exercise. Resting SVR in the CHF group was higher <