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CLINICAL STUDIES

Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment?

^a Division of Cardiology, University Hospital, Bern, Switzerland

Manuscript received June 29, 1998; revised manuscript received September 17, 1998, accepted December 15, 1998.

Reprint requests and correspondence: Dr. Christian Seiler, Cardiology, University Hospital, Inselspital, Freiburgstrasse, CH-3010 Bern, Switzerland
christian.seiler{at}insel.ch

OBJECTIVES

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.

BACKGROUND

The development of myocardial tolerance to repeated ischemia is nowadays interpreted to be due to biochemical adaptation (i.e., ischemic preconditioning).

METHODS

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).

RESULTS

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; CFI) and the respective ST elevation shift (ST):

CONCLUSIONS

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.

Abbreviations and Acronyms   CAD = coronary artery disease   CFI = collateral flow index   CR = collateral recruitment   CVP = central venous pressure   ECG = electrocardiography   i.c. = intracoronary   IT = ischemic tolerance (of the myocardium)   P = (ischemic) preconditioning   Pao = (mean) aortic pressure   Poccl = distal coronary artery pressure during balloon occlusion (coronary wedge pressure)

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