Quantification of ischemic stress during repeated coronary artery occlusion in the dog A method for validation of therapeutic effects

Summary

As criterion for the degree of ischemic stress on myocardium during repeated cronary artery occlusion, the reproducibility of the release of potassium, lactate and inorganic phosphate in the early reperfusion period was examined.

On 20 anaesthetized open-chest mongrel-dogs, local ischemia was induced by intermittent occlusion of the LAD artery. In each experiment the artery was occluded for 3 min 4 to 6 times with intervals of 45 min. Just before beginning, at the end of occlusion and after 5 min of reperfusion, arterial and coronary venous blood was collected simultaneously. Additionally, 3 ml of blood were withdrawn by syringe-pumps during the first minute of reperfusion.

Intraindividually, the following standard-deviations were found in a representative experiment with 5 occlusions: potassium ±7% (22.62±1.6 μmol/min); inorganic phosphate ±9% (19.82±2.06 μmol/min); lactate ±11% (55.38±5.93 μmol/min).

Interindividually, the correlation between the release of these markers and the perfusion bed of the ligated artery led to coefficients of about r∼0.88. On an average, per gram ischemic tissue/wet weight 0.74 μmol potassium, 0.6 μmol inorganic phosphate and 1.98 μmol lactate were released. The ratios between the releases remained constant independent of the size of ischemic area. An even closer correlation with coefficients of about r∼0.97 was found between the releases and the O₂-debt in the occlusion period.

Based on a synoptic assessment of metabolic and energetic parameters, this experimental model may render more detailed information on pharmacological interventions during ischemic stress.