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Influence of neutrophil depletion on myocardial function and flow after reversible ischemia
P G O'Neill1, M L Charlat, L H Michael
1Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Abstract:
We explored the role of polymorphonuclear leukocytes (PMN) in the genesis of contractile dysfunction (myocardial "stunning") and of vascular abnormalities after reversible ischemia. Open-chest dogs underwent a 15-min coronary occlusion and 4 h of reperfusion (REP); treated animals (n = 16) received intravenous goat antiserum against canine PMN, whereas controls received nonimmune goat serum (n = 10) or saline (n = 15). In treated dogs, the average blood PMN levels were 10% of those in saline controls. During ischemia, collateral flow tended to be higher, and paradoxical systolic wall thinning tended to be less in neutropenic dogs, but despite this, recovery of wall thickening after REP was not enhanced in these animals. Similarly, arrhythmias during ischemia or REP did not differ among the three groups. Four hours after REP, both resting and minimal coronary resistance (the latter assessed by adenosine infusion) were higher in the stunned compared with the nonischemic myocardium; these vascular derangements, however, were similar in all three groups. Thus profound neutropenia failed to attenuate mechanical dysfunction, to reduce arrhythmias, and to prevent vascular abnormalities after a 15-min coronary occlusion. Although previous studies have suggested that neutrophils mediate cell death during prolonged ischemia, the present findings suggest that PMN do not contribute importantly to the damage associated with brief, reversible ischemia. The duration of flow reduction may be a critical factor determining whether PMN exacerbate ischemic injury.
Insights
Polymorphonuclear leukocytes (PMN) did not significantly impact myocardial stunning or vascular issues after brief ischemia. Reducing PMN levels did not improve heart function recovery or prevent damage in this study.
Area of Science:
- Cardiovascular Physiology
- Inflammation and Immunology
- Ischemic Heart Disease
Background:
- Polymorphonuclear leukocytes (PMN) are implicated in tissue damage following ischemia.
- The precise role of PMN in myocardial stunning and vascular dysfunction after reversible ischemia remains unclear.
Purpose of the Study:
- To investigate the role of PMN in myocardial contractile dysfunction and vascular abnormalities after brief, reversible coronary artery occlusion.
- To determine if reducing PMN levels mitigates damage and improves recovery following ischemic events.
Main Methods:
- Open-chest dogs underwent 15 minutes of coronary occlusion followed by 4 hours of reperfusion.
- Animals received either anti-PMN antiserum (to induce neutropenia), nonimmune goat serum, or saline.
- Myocardial function, arrhythmias, collateral flow, and coronary vascular resistance were assessed.
Main Results:
- Profound neutropenia (PMN levels at 10% of controls) did not enhance the recovery of myocardial wall thickening after reperfusion.
- Neutropenic dogs did not show reduced arrhythmias or prevent vascular derangements (increased coronary resistance) compared to controls.
- Despite trends towards higher collateral flow and less wall thinning during ischemia in neutropenic dogs, overall recovery was not improved.
Conclusions:
- PMN do not appear to play a significant role in the mechanical dysfunction, arrhythmias, or vascular abnormalities associated with brief (15-minute) reversible myocardial ischemia.
- The duration of ischemic flow reduction may be a critical factor in determining the contribution of PMN to ischemic injury.
- These findings suggest that interventions targeting PMN may not be beneficial for short-term ischemic events.