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Capillary perfusion in the occluded-reperfused canine myocardium: evidence for slowed reflow
1Department of Physiology and Biophysics, UMDNJ--Robert Wood Johnson Medical School, Piscataway 08854-5635.
Insights
The no-reflow phenomenon after heart reperfusion is functional, not anatomical. Sluggish, clustered capillary perfusion, not physical obstruction, explains reduced blood flow in the occluded heart region.
Area of Science:
- Cardiovascular Physiology
- Ischemia-Reperfusion Injury
- Microcirculation Research
Background:
- The no-reflow phenomenon is a critical complication following myocardial ischemia and reperfusion.
- Distinguishing between anatomical obstruction and functional perfusion deficits is crucial for understanding this phenomenon.
Purpose of the Study:
- To investigate whether the no-reflow phenomenon in the canine heart after occlusion and reperfusion is due to physical blockage of capillaries or impaired blood flow.
- To differentiate between anatomical and functional causes of reduced perfusion in ischemic myocardium.
Main Methods:
- Isolated canine left anterior descending (LAD) coronary artery occlusion (2 hours) followed by reperfusion (4 hours).
- Injection of fluorescently labeled dextran in multiple pass (MP) or single pass (SP) circulation protocols.
- Quantification of perfusable capillaries versus FITC-dextran perfused microvessels in myocardial sections using immunohistochemistry.
Main Results:
- No significant difference in the total perfusable capillary bed between control and LAD regions in the MP group.
- A significant reduction in the percentage of perfused capillaries in the LAD region compared to control in the SP group.
- Perfusion distribution in the LAD region of the SP group was random, clustered, and more dispersed than the control region.
Conclusions:
- The findings argue against physical obstruction of the capillary bed as the cause of the no-reflow phenomenon.
- The data strongly suggest that sluggish and clustered capillary perfusion during a single pass of circulation underlies the no-reflow phenomenon in occluded-reperfused myocardium.
Abstract:
The purpose of this study was to determine if the no-reflow phenomenon in the occluded/reperfused dog heart was anatomical (capillary bed could not be perfused) or functional (slowed capillary perfusion). The left anterior descending (LAD) coronary artery was isolated in anesthetized open-chest dogs. The LAD was occluded (2 hr) then reperfused (4 hr). A total of 14 dogs were assigned to one of two groups: The multiple pass (MP) or single pass (SP) group. Fluorescent labeled dextran (FITC) was injected and circulated either for 10 min in the MP group or for one pass of the circulation in the SP group. In the last 2 min, the MP group was asphyxiated. Hearts were excised and frozen in liquid nitrogen. The LAD and control region were isolated and frozen sections (5 microns) obtained. Sections were photographed under fluorescent light and then immunohistochemically stained. The microvessels were identified by visualizing the endothelium with a Factor VIII antibody. The specific areas photographed were relocated. The total number of capillaries, determined by stain outlining a lumen of no greater than 10 microns in diameter, were counted. This number was compared to the number of microvessels containing FITC-dextran. There was no difference in the total perfusable capillary bed in the MP group between the control and LAD regions (80 +/- 4 and 82 +/- 10%). In the SP group, there was a significant difference between the control and LAD regions (59 +/- 25 and 46 +/- 14%). The percentage of the capillary bed perfused in the SP group was less than the MP group in each region. Closest individual analysis of the perfused capillary distribution in the SP group, showed the distribution in the LAD region was random, potentially clustered and more dispersed compared to the control region. This study provides data against physical obstruction of the capillary bed secondary to ischemia. The data suggest sluggish and clustered perfusion in the occluded-reperfused myocardium during a single pass of the coronary circulation.