The purpose of this study in patients with quantitatively determined, poorly developed
coronary collaterals was to assess the contribution of ischemic as well as adenosine-induced
preconditioning and of collateral recruitment to the development of tolerance against
repetitive myocardial ischemia.
The development of myocardial tolerance to repeated ischemia is nowadays interpreted
to be due to biochemical adaptation (i.e., ischemic preconditioning).
In 30 patients undergoing percutaneous transluminal coronary angioplasty, myocardial
adaptation to ischemia was measured using intracoronary (i.c.) electrocardiographic
(ECG) ST segment elevation changes obtained from a 0.014-in. (0.036 cm) pressure guidewire
positioned distal to the stenosis during three subsequent 2-min balloon occlusions.
Simultaneously, an i.c. pressure-derived collateral flow index (CFI, no unit) was
determined as the ratio between distal occlusive minus central venous pressure divided
by the mean aortic minus central venous pressure. The study patients were divided
into two groups according to the pretreatment with i.c. adenosine (2.4 mg/min for
10 min starting 20 min before the first occlusion, n = 15) or with normal saline (control
group, n = 15).
Collateral flow index at the first occlusion was not different between the groups
(0.15 +/- 0.10 in the adenosine group and 0.13 +/- 0.11 in the control group, p =
NS), and it increased significantly and similarly to 0.20 +/- 0.14 and to 0.19 +/-
0.10, respectively (p < 0.01) during the third occlusion. The i.c. ECG ST elevation
(normalized for the QRS amplitude) was not different between the two groups at the
first occlusion (0.25 +/- 0.13 in the adenosine group, 0.25 +/- 0.19 in the control
group). It decreased significantly during subsequent coronary occlusions to 0.20 +/-
0.15 and to 0.17 +/- 0.13, respectively. There was a correlation between the change
in CFI (first to third occlusion; deltaCFI) and the respective ST elevation shift
(deltaST): deltaST = -0.02 to 0.78 x deltaCFI; r = 0.54, p = 0.02.
Even in patients with few coronary collaterals, the myocardial adaptation to repetitive
ischemia is closely related to collateral recruitment. Pharmacologic preconditioning
using a treatment with i.c. adenosine before angioplasty does not occur. The variable
responses of ECG signs of ischemic adaptation to collateral channel opening suggest
that ischemic preconditioning is a relevant factor in the development of ischemic
tolerance.