Hemodynamic factors limiting the response to transdermal nitroglycerin in severe chronic congestive heart failure

To clarify the continuing controversy concerning the use of transdermal nitroglycerin (MN), the short-term hemodynamic responses to sublingual, oral and transcutaneous nitrates were evaluated and compared in 22 patients with severe chronic congestive heart failure. Sixteen patients showed favorable hemodynamic effects with TDN, but the doses needed to achieve this response varied greatly: 10 mg/24 hours in 6 patients, 20 mg/24 hours in 5 patients, 40 mg/24 hours in 3 patients and 60 mg/24 hours in 2 patients. Of the 6 remaining patients, 3 did not respond to high-dose TDN even though they showed marked effects after sublingual and oral nitrate administration; 3 others did not respond to any nitrate formulation by any route. TDN produced immediate increases in cardiac index and decreases in right and left ventricular filling pressure, mean arterial pressure and systemic vascular resistance (p < 0.01). These effects, however, became rapidly attenuated within 3 to 6 hours; hours; after 18 to 24 hours, only modest decreases in right and left ventricular filling pressures were observed. After removal of TDN treatment, rebound decreases in cardiac index and rebound increases in mean arterial pressure and systemic vascular resistance occurred, but right and left ventricular filling pressures returned to pretreatment values without rebound changes. isosorbide dinitrate, 40 mg orally, produced hemodynamic effects that were greater in magnitude than effects seen after administration of TDN (p < 0.05 to 0.01), but 4 patients in whom tolerance to TDN developed showed reversible cross tolerance to oral isosorbide dinitrate. In conclusion, the use of TDN in patients with severe chronic congestive heart failure is limited by the large doses of the drug that are needed in some patients, by the rapid attenuation of its beneficial effects during prolonged therapy, by the potential for cross tolerance to other nitrates, and by the occurrence of rebound phenomena after drug withdrawal.