Low- and high-blood flow regions in the normal pig heart are equally vulnerable to ischaemia during partial coronary stenosis

Abstract

Myocardial perfusion is heterogeneous, even in the normal heart. It is unknown whether the resting normal blood flow level predicts the severity of mismatch between local blood flow and metabolism during acute ischaemia. In the present study local blood flow (measured with radioactively labelled microspheres) and metabolic indicators of ischaemia [tissue contents of lactate and inosine (INO), a breakdown product of adenosine triphosphate (ATP)] were determined in 84-102 simultaneously frozen samples (approximately 0.9 g) of normal (n = 7) and partially ischaemic (n = 4) porcine left ventricles. Ischaemia was induced for 20 min by partially occluding the left anterior descending artery to reduce perfusion pressure from 107 +/- 17 mm Hg to 39 +/- 10 mm Hg (mean +/- SD). Flow reduction in the ischaemic region was strongly variable, both within the subepicardium (range 6-66%, average 34%) and the subendocardium (range 33-84%, average 57%), indicating redistribution of blood flow inside transmural layers in addition to the well-known preferential decrease in subendocardial perfusion. The relative flow reduction during stenosis was not dependent on normal local perfusion level (Spearman rank correlation coefficient -0.002, P = 0.99). Samples with low or high myocardial blood flows before stenosis showed similar increases in lactate content and INO/ATP content ratio, as long as the percentage blood flow reduction was the same. It is concluded that regions with low and high resting flows in the normally perfused heart are equally susceptible to metabolism-perfusion mismatch resulting from coronary stenosis.

Spatial heterogeneity of energy turnover in the heart

“…The considerable spatial heterogeneity of energy turnover demonstrated in the present study may also explain the recent finding that during low-flow ischemia there is no uniform flow threshold for biochemical markers of ischemia (adenosine, inosine, lactate) to rise [3,20]. In contrast, only when the individual local flow decreased by approximately 50% did adenosine and lactate increase.…”

Myocardial O2consumption in porcine left ventricle is heterogeneously distributed in parallel to heterogeneous O2delivery

“…Low-flow areas had lower V O 2 and highflow areas had higher V O 2 . Further studies showed that areas of the left ventricle that receive a relatively low amount of blood flow are not in a hypoxic state, suggesting local adaptation of blood flow to oxygen demand (8,11,14). However, direct measurement of aerobic metabolic flux in small myocardial regions became possible only recently.…”

Progressively heterogeneous mismatch of regional oxygen delivery to consumption during graded coronary stenosis in pig left ventricle

“…Previous studies showed that regions of high blood flow and metabolic demand, as determined under basal conditions without coronary constriction, are metabolically stressed to a similar extent during hypoperfusion as regions with a low basal blood flow (9,27). Tissue damage following severe ischemia is more frequent in regions with high blood flow under normal conditions (19), which may be related to the higher metabolic rate in these regions.…”

“…The vulnerability of low-vs. high-control blood flow regions has been investigated previously (9,19,27). Here, we plotted oxygen extraction against basal blood flow at t ϭ 0 (Fig.…”

“…Increased oxygen extraction might be expected a priori during stenosis in regions that show a higher control blood flow before stenosis because high flow correlates with high metabolic demand in the normal myocardium (19). Although lactate and inosine, breakdown products of ATP, were shown not to accumulate significantly more during stenosis in regions with higher basal blood flow (9), this has so far never been investigated at the level of metabolic fluxes. Therefore, we examine how oxygen extraction during stenosis depends on the basal blood flow level before stenosis.…”