Delayed preconditioning-mimetic action of nitroglycerin in patients undergoing coronary angioplasty.
BACKGROUND
Experimental studies suggest that the cardioprotective effects of the late phase of ischemic preconditioning (PC) can be mimicked pharmacologically. However, to date, no drug has been tested with respect to its ability to elicit a late PC effect in humans. As a consequence, clinical exploitation of the powerful anti-stunning and anti-infarct actions of late PC has been elusive thus far.


RESULTS
A total of 66 patients were randomized to receive a 4-hour intravenous infusion of nitroglycerin (NTG) or normal saline; on the following day, they underwent percutaneous transluminal coronary angioplasty (three 2-minute balloon inflations 5 minutes apart). Measurements of ST-segment shifts (intracoronary and surface ECGs), regional wall motion (quantitative 2D echocardiography), and chest pain score indicated that the infusion of NTG 24 hours before angioplasty rendered the myocardium relatively resistant to ischemia and that the degree of this cardioprotective effect was comparable to that afforded by the ischemia associated with the first balloon inflation in control subjects (early phase of ischemic PC). Collateral flow (estimated from a pressure-derived index) did not differ between control and NTG-pretreated patients, indicating that the enhanced tolerance to ischemia in NTG-pretreated patients cannot be accounted for by baseline differences in collateral function.


CONCLUSIONS
NTG protects human myocardium against ischemia 24 hours after its administration. To the best of our knowledge, this is the first report that a late PC effect can be recruited pharmacologically in humans. The results suggest that prophylactic administration of nitrates could be a novel approach to the protection of the ischemic myocardium in patients.
Leesar
M A
MA
Division of Cardiology, University of Louisville, and Jewish Hospital Heart and Lung Institute, Louisville, KY, USA.
Stoddard
M F
MF
Dawn
B
B
Jasti
V G
VG
Masden
R
R
Bolli
R
R
D015906:Angioplasty, Balloon, Coronary; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002637:Chest Pain / Q000188:drug therapy; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000175:diagnosis / Q000628:therapy*; D004452:Echocardiography; D004562:Electrocardiography / Q000187:drug effects; D006334:Heart Function Tests / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D009203:Myocardial Infarction / Q000517:prevention & control; D017682:Myocardial Stunning / Q000517:prevention & control; D005996:Nitroglycerin / Q000008:administration & dosage*; D016037:Single-Blind Method; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage; D016277:Ventricular Function, Left / Q000187:drug effects
D014665:Vasodilator Agents; D005996:Nitroglycerin