Effects of isosorbide dinitrate on electrocardiography, hemodynamics, and ventilation in patients with exercise-induced elevation of pulmonary arterywedge pressure

Background: The mechanisms underlying exertional hyperpnea in patients with coronary artery disease and transient left ventricular dysfunction are sti ll not fully understood. Hypothesis: The study was undertaken to investigate whether the ventilatory response to exercise reflects the effects of acute medical treatment of ex ercise-induced left ventricular dysfunction, and to evaluate mechanisms rel evant to excessive exertional ventilation. Methods: In 11 male patients, aged 65.2 +/- 6.0 years, all with pulmonary a rtery wedge pressure (PAWP) > 25 mmHg and ST depression > 2 mm during moder ate supine exercise, ventilation (V), oxygen uptake (V-O2), hemodynamics, e lectrocardiogram (ECG), and arterial and mixed venous blood gases were exam ined during supine rest and exercise, before and at hourly intervals after peroral intake of 30 mg isosorbide dinitrate (ISDN). Six similar patients w ere examined with the same protocol without ISDN administration and compris ed a control group. Results: Before administration of ISDN, exercise PAWP was 35.3 +/- 5.9 mmHg , ECG showed 2.77 +/- 1.06 mm ST depression, and V/V-O2, was 31.8 +/- 4.8 l /l. One h after ISDN administration, exercise mean PAWP was 11.0 +/- 2.5 mm Hg (p < 0.001), ST depression 0.59 +/- 0.8 mm (p < 0.001), whereas V/V-O2 w as unchanged, 30.1 +/- 5.3 l/l. Two h later, PAWP remained reduced and ther e were only minor ST depressions, while V/V-O2 remained high. Exercise card iac index (CI) and mixed venous oxygen tension (PVO2), initially 4.7 +/- 0. 67 l/min/m(2) and 3.54 +/- 0.35 kPa, respectively, remained at the same low level throughout the study. In the six nontreated patients, there were no significant changes in ST depression, exercise PAWP, or exertional ventilat ion. Conclusion: Isosorbide dinitrate treatment markedly improved exercise-induc ed left heart dysfunction, whereas excessive ventilatory response was unaff ected, even after 3 h. Thus, measurements of the exercise hyperpnea did not properly reflect effective reduction of myocardial ischemia.