No evidence for ischemic preconditioning during repeated vessel occlusion in coronary angioplasty

Coronary angioplasty has been the favoured model in studying ischemic preconditioning in humans, but results have remained controversial, possibly due to some artefacts related to coronary balloon angioplasty as an ischemia model. We examined this issue by monitoring the sequential metabolic, functional and neurohumoral changes during repeated vessel occlusion in coronary angioplasty performed in patients with chronic angina pectoris. Two groups of patients undergoing two successive balloon inflations of approximately 2 min duration were studied. These balloon inflations were preceded by a short inflation performed immediately after introduction of the balloon into the stenosis. The aim of this primary inflation was to establish adequate coronary blood flow with the deflated balloon in the stenosis and to guarantee that the subsequent two balloon inflations were truly comparable in time. Group I consisted of 23 patients, in whom the changes in the degree of angina, pulmonary capillary wedge pressure (PCWP), atrial natriuretic peptide (ANP) and circulating catecholamines during the procedure were studied. The sequential changes in myocardial metabolism were monitored in group II of nine patients by determining the lactate extraction ratios and femoroarterial coronary sinus (Fa-CS) differences in pH and pCO2 before and after each balloon inflation. In group I, PCWP and total catecholamines increased similarly during both balloon inflations, but ANP remained unchanged. In group II patients the lactate extraction ratios turned negative, the Fa-CS pH-differences increased and the pCO2-differences decreased during vessel occlusions, the changes being somewhat more prominent during the second balloon inflation. To study adaptation to ischemia, the group I patients were divided into two subgroups with and without signs of ischemic dysfunction during balloon inflations (PCWP increase > 5 mmHg and < 5 mmHg, respectively), and the group II patients were divided into two subgroups with and without metabolic ischemia (lactate-producers and non-producers). The ANP levels were constantly higher in the patients demonstrating ischemic dysfunction during balloon inflations, but catecholamine levels increased only after the second balloon inflation. The anginal pain experienced by the patients and the signs of metabolic ischemia were identical during both balloon inflations. We conclude that acute ischemic preconditioning does not occur in patients with repeated vessel occlusions of approximately 2 min duration. The patients without ischemia during the procedure had more critical stenoses and pre-existing collaterals. However, other protective mechanisms, such as chronic adaptation at the cellular level or recruitment of new collaterals, cannot be excluded.