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 (TDN), the shortterm 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 less than 0.01). These effects, however, became rapidly attenuated within 3 to 6 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 less than 0.05 to 0.01), but 4 patients in whom tolerance to TDN developed showed reversible cross tolerance to oral isosorbide dinitrate.(ABSTRACT TRUNCATED AT 250 WORDS)
Packer
M
M
Medina
N
N
Yushak
M
M
Lee
W H
WH
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D005996:Nitroglycerin; D007548:Isosorbide Dinitrate