• Hemodynamic monitoring revealed a clear improvement in pre- and afterload parameters for both drugs (p < 0.01 & p < 0.001), while captopril induced a higher increase in cardiac index (+49.2% vs. +25%), stroke volume index (+53.5% vs. +25.7%), and stroke work index (+55% vs. +28%) than nitroglycerin (P less than 0.001).
  
• The onset of change for most hemodynamic parameters was measured earlier after nitroglycerin (after 12-19 vs. 16-22 mins). Captopril revealed later peak effects (after 47-84 vs. 25-55 min, p < 0.001) and a longer sustained improvement in hemodynamic values (return to baseline values after 117-162 vs. 68-120 min, p < 0.001).
  
• No side effects occurred after either captopril or nitroglycerin.

Prospective, Single-Center Study

Patients with LVFP (pulmonary wedge pressure) over 14 mm Hg were given chewable isosorbide dinitrate (CHIS) 10 mg, SL NTG, 0.6 mg, and placebo, two chewable tablets, in random fashion

• Heart rate was not significantly affected by any drug, although it rose slightly after SL NTG and fell after CHIS.
  
• Significant reduction of BP occurred only after SL NTG, with peak effect at 5 minutes, but lasting only 15 minutes.
  
• SL NTG reduced LVFP 5.1 mm Hg (19.5%, p< 0.05), at peak effect, but LVFP was no longer significantly lower by 20 mins after SL NTG.
  
• After CHIS, LVFP fell significantly within 5 min, reached a peak reduction of 8.6 mm Hg (32;7%, p < 0.01) at 15 minutes, and remained significantly lower through 3 hrs.

Chewable isosorbide dinitrate provides a nitrate action of rapid onset and sustained effect that may be useful for chronic vasodilator therapy of heart failure.

• Group A:  n = 7 had hemodyamic evaluation after receiving 1.6 mg SL NTG
  
• Group B:  n = 15 received doses between 0.8 - 2.4 mg SL NTG where the clinical course was documented

Group A:

• Within 10 mins after 1.6 mg SL NTG, left ventricular filling pressure decreased from 33 ± 10 (mean ± 1 standard deviation) to 24 ± 8 mm Hg, and cardiac output increased significantly from 3.3 ± 0.8 to 3.7 ± 0.8 liters/min.
  
• In one patient with recent MI, LV filling pressure decreased from 50 to 27 mm Hg within 5 minutes.
  
• Orthopnea and pulmonary rales disappeared rapidly. 

Group B:

• 5 mins after administration, the first evidence of clinical improvement was observed in seven of these patients.
  
• After 15 to 20 minutes, pulmonary rales disappeared or decreased in 11 and dyspnea decreased in 14.
  
• The elevated arterial blood pressure and heart rate decreased significantly.
  
• Only one patient with terminal pulmonary edema remained refractory to therapy
  

Center of Internal Medicine, Department of Cardiology, University of Frankfurt/Main, West Germany

The patients received, in a random order:

• ISDN spray 2.5 mg
• Sublingual NTG 0.8 mg

• Hemodynamic measurements were performed before and at 1, 3, 5, 10, 20, 30 and 60 minutes after each drug
  
• The second drug was given only after return of the hemodynamic parameters to baseline, plus a washout period of 2 hours

• Both drugs produced hemodynamic improvement including a decrease in pulmonary capillary wedge pressure (PCWP), right atrial pressure and systemic and pulmonary vascular resistances.
  
• Only ISDN spray significantly increased cardiac output.
  
• The onset of action of ISDN spray was significantly more rapid than that of NTG. This was primarily evident in the decrease in PCWP. With ISDN spray the decrease started at 1 minute after administration, and at 3 minutes a decrease of 8.6 mm Hg was already found. The corresponding value for sublingual NTG was 1.6 mm Hg. The difference was highly significant (p less than 0.02).
  
• The peak effect of ISDN spray on PCWP and right atrial pressure was greater than that of NTG.

The onset of the hemodynamic effect of ISDN spray is much more rapid than that of sublingual NTG tablets. At the doses used, the magnitude of the effect of the ISDN spray on some of the hemodynamic variables is greater than that of sublingual NTG.

n = 37;  patients had unstable angina under resting, pain free conditions

• n = 8; Sublingual NTG 0.4 mg
  
• n = 7; Isosorbide dinitrate 20 mg
  
• n = 7; Placebo

• There was a significant (p < 0.05 or < 0.1) reduction of the MAP (5 to 10 mm Hg) that persisted for > 4 hrs following both sublingual and oral administration of isosorbide dinitrate.
• The changes in the PAEDP, HR, and CI following sublingual or oral administration of isosorbide dinitrate were small and not significant.
  
• In the group receiving isosorbide dinitrate sublingually, the EDV was reduced by more than 30 ml below the placebo group (p < 0.1) for up to 4 hrs.
  
• The effects of nitroglycerin administration were similar in magnitude but of much shorter duration (3 to 4 hrs for sublingual and oral administration of isosorbide dinitrate vs 15 to 30 mins for nitroglycerin).

The hemodynamic effects of sublingually and orally administered isosorbide dinitrate in patients with unstable angina pectoris and normal resting hemodynamics is 8 to 12 times longer than that of nitroglycerin.