Effects of nifedipine and nitroglycerin on left ventricular systolic dysfunction and impaired diastolic filling after exercise-induced ischemia in humans.
OBJECTIVE
This study sought to determine whether calcium antagonist, compared with nitroglycerin, administration attenuates left ventricular dysfunction after exercise-induced ischemia in humans.


BACKGROUND
Exercise-induced ischemia impairs left ventricular systolic function and diastolic filling after exercise. The mechanism of this phenomenon is unknown but may relate to intracellular calcium overload.


METHODS
Echocardiography was performed in 131 patients before and 30 min, 2 h and 4 h after exercise stress test. Ischemia was defined as a reversible thallium stress defect. No medication, sublingual nitroglycerin or nifedipine was randomly given to each patient at peak exercise.


RESULTS
Isovolumetric relaxation time was significantly prolonged from rest (100 +/- 19 ms [mean +/- SD]) to 30 min (118 +/- 20 ms, p < 0.0005), 2 h (117 +/- 18 ms, p < 0.0005) and 4 h (110 +/- 22 ms, p < 0.05) after exercise in 21 patients with exercise-induced ischemia who received no medication (ischemia-none group). Isovolumetric relaxation time similarly increased after exercise in 23 patients who received nitroglycerin and had exercise-induced ischemia (ischemia-NTG group) but was unchanged in 20 patients with exercise-induced ischemia who received nifedipine (ischemia-nifedipine group). Peak early filling velocity decreased in the ischemia-none and ischemia-NTG groups from rest to 30 min and 2 h after exercise, but peak early filling velocity was unchanged in the ischemia-nifedipine group. Ejection fraction decreased from rest to 30 min after exercise in the ischemia-none group (59 +/- 12% vs. 51 +/- 13%, p < 0.025) and ischemia-NTG group (59 +/- 14% vs. 49 +/- 14%, p < 0.005) but was unchanged in the ischemia-nifedipine group (60 +/- 19% vs. 64 +/- 18%, p = NS). A new regional left ventricular wall motion abnormality occurred more frequently 30 min after exercise in the ischemia-none group (11 [52%] of 21) and ischemia-NTG group (9 [39%] of 23) compared with the ischemia-nifedipine group (2 [10%] of 20, both p < 0.05). No change occurred in left ventricular systolic function and diastolic filling after exercise in the control groups.


CONCLUSIONS
Exercise-induced ischemia impairs systolic function and diastolic filling after exercise. Sublingual nifedipine but not nitroglycerin attenuates this process and suggests that altered calcium homeostasis may play a role in left ventricular dysfunction that occurs after exercise-induced ischemia.
Stoddard
M F
MF
Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.
Wagner
S G
SG
Ikram
S
S
Longaker
R A
RA
Prince
C R
CR
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000627:therapeutic use*; D013599:Systole / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D005996:Nitroglycerin; D009543:Nifedipine