Inhaled Nitric Oxide Modifies Left Ventricular Diastolic Stress in the Presence of Vasoactive Agents in Heart Failure

Abstract

Nitric oxide (NO) inhalation therapy has been widely used in several diseases with pulmonary hypertension. However, application of NO inhalation therapy remains controversial in heart failure. Cardiovascular effects of inhaled NO (iNO) were evaluated in dogs before and after induction of heart failure with and without infusion of vasoactive agents. iNO did not affect the baseline left ventricular (LV) function or the response to isoproterenol in control conditions or heart failure induced by procainamide. Pulmonary vascular resistance was significantly decreased by iNO in heart failure with infusion of vasoactive agents. Unexpectedly, LV end-diastolic pressure was significantly elevated by iNO in heart failure in the presence of infusion of vasoactive agents independent of their types; either the vasodilating agents of acetylcholine and nitroglycerin or the vasoconstricting agents of norepinephrine and angiotensin-II. The end-diastolic LV dimension and wall stress were also significantly increased by iNO, however, those at end systole were not affected. These results suggested that NO inhalation therapy reduced pulmonary vascular resistance, whereas in the presence of additional stress of vasoactive agents, it increased LV preload and end-diastolic wall stress in heart failure.

Unequal effects of renin-angiotensin system inhibitors in acute cardiac dysfunction induced by isoproterenol

“…Importantly, the positive inotropic response to ␤-adrenergic stimulation is known to be suppressed by NO (18,42,43). We have previously demonstrated that LV dysfunction is indirectly aggravated even with inhaled NO in heart failure (32).…”

Inhaled nitric oxide versus aerosolized iloprost for the treatment of pulmonary hypertension with left heart disease*

“…This seeming disregard for the use of inhaled vasodilators in the large patient population with CHF is primarily based on the results of earlier clinical trials with systemic vasodilators, such as nifedipine, oral milrinone, flosequinan, or epoprostenol (Flolan), which failed to show therapeutic benefit and frequently even worsened clinical outcome (10 -12, 21). Adverse systemic or pulmonary effects including hypotension with reduced coronary perfusion (22), left ventricular volume overload (14), or pulmonary edema formation by opening of precapillary sphincters in the lung (13) may have contributed to these detrimental results. Albeit the cause for these therapeutic failures remains incompletely understood, the studies identify systemic afterload reduction as a delusive strategy for the treatment of patients with CHF.…”

“…Because systemic administration of vasodilators in CHF yielded detrimental results in several clinical trials (10 -12), we further speculated that inhalative delivery may be superior due to its relative selectivity for the pulmonary vasculature. A major concern for the use of inhaled vasodilators in CHF are potential side effects, which include edema formation due to the opening of precapillary sphincters (13) or left ventricular volume overload (14). Hence, systematic studies on the putative benefits and adverse effects of inhaled vasodilators in pulmonary hypertension with left heart disease are required.…”

Magnesium attenuates isoproterenol-induced acute cardiac dysfunction and β-adrenergic desensitization

“…LV pressure, the rate of LV pressure change (LV dP/dt), and the time constant of LV isovolumic relaxation () were measured by a catheter-tipped transducer (PC-350; Millar, Houston, TX) inserted from the right carotid artery into the LV. A 5-MHz single-plane transducer for transesophageal echocardiography (SSD-830; Aloka, Tokyo, Japan) was placed just behind the LV to monitor changes in LV dimensions (29).…”