doi: 10.1161/01.CIR.0000037128.03240.41
(Circulation. 2002;106:e143.)
© 2002 American Heart Association, Inc.
Correspondence |
No-Reflow Phenomenon
Anatomical Pathology, SUNY Upstate Medical University, Syracuse, NY, E-mail hellstrr@mail.upstate.edu
To the Editor:
In reviewing no-reflow, Rezkalla and Kloner1 indicted injury-induced microvascular changes, but did not mention spasm of resistance vessels, which might be the basic mechanism of no-reflow. I proposed in 1971 that no-reflow ("stasis") is due to ischemic injury-induced spasm, and the evidence seemed convincing.2 Short coronary occlusions reversed no-reflow, and this was interpreted as reversal of spasm; occlusion-induced ischemia caused reactive hyperemia, which reversed spasm. The ability to alternate repeatedly between normal and low flows seemed to rule out mechanisms as cell swelling, microvascular obstruction by white cells and platelets, and vascular damage directly causing no-reflow.
Reduced flow (ie, no-reflow) has been attributed by Gregorini et al3 to vasoconstriction in individuals treated with percutaneous transluminal coronary angioplasty (PTCA), cases which support the spastic cause of no-reflow. In cases reported in 1999,3 no-reflow was due to infarction (no-reflow present before PTCA); in cases reported in 1998 and discussed in the 1999 paper,3 no-reflow followed the ischemic insult of PTCA in individuals without infarction. I attribute no-reflow in these cases to spasm from the acute ischemic injury of infarction or PTCA, plus chronic ischemic injury from coronary stenoses. The often sudden and dramatic onset of no-reflow in infarction after short-term interventions1 is consistent with a spastic response to fresh ischemic injury; no-reflow soon after brief ischemic episodes seems poorly explained by microvascular obstruction by cell swelling or cellular elements.
The study by Gregorini et al3 support reversal of no-reflow by short coronary occlusions. Post-infarct mild no-reflow was reversed by PTCA for 15 minutes, after which no-reflow returned, and this is explained by reactive hyperemia generated by PTCA-induced ischemia; reactive hyperemia reversed spasm until vasodilation dissipated, allowing spasm to reoccur. Also, in cases without infarction, no-reflow occurred 15 minutes after PTCA; delay in developing no-reflow is explained by reactive hyperemia, which reversed spasm until vasodilation dissipated.
Occurrence of systolic flow reversal with no-reflow4 is highly consistent with the spastic cause of no-reflow; this phenomenon was demonstrated during spontaneous angina in microvascular angina,5 which has been attributed to spasm.5 One tracing of the 1971 study2 showed reversed systolic flow, and its limited demonstration is attributed to insensitivity of earlier flow measurement techniques.
Consistent with the mechanism of spasm, verapamil and adenosine improve no-reflow.1 Also, 
-adrenergic blockade, which operates against ischemia-induced spasm, reversed no-reflow in cases associated and unassociated with infarction.3 Because -adrenergic blockade reversed no-reflow,3 this modality might be useful in preventing and treating no-reflow.
References
- Rezkalla SH, Kloner RA. No-reflow phenomenon. Circulation. 2002; 105: 656–662.
[Free Full Text]
- Hellstrom HR. Coronary artery stasis after induced myocardial infarction in the dog. Cardiovasc Res. 1971; 5: 371–375.[Medline]
[Order article via Infotrieve]
- Gregorini L, Marco J, Kozàkovà M, et al. -adrenergic blockade improves recovery of myocardial perfusion and function after coronary stenting in patients with acute myocardial infarction. Circulation. 1999; 99: 482–490.
[Abstract/Free Full Text]
- Akasaka T, Yoshida K, Kawamoto T, et al. Relation of phasic coronary flow velocity characteristics with TIMI perfusion grade and myocardial recovery after primary percutaneous transluminal coronary angioplasty and rescue stenting. Circulation. 2000; 101: 2361–2367.
[Abstract/Free Full Text]
- Takeuchi M, Kuroiwa A. Alteration of coronary flow velocity during spontaneous angina in a patient with microvascular angina. Cathet Cardiovasc Intervent. 2000; 50: 63–67.[CrossRef][Medline]
[Order article via Infotrieve]
Response
Marshfield Clinic, Marshfield, Wis
The Heart Institute, Good Samaritan Hospital, Los Angeles, Calif
We thank Dr Hellstrom for his interest in our article1 and agree that small vessel spasm may be yet another mechanism that could contribute to no-reflow. However, the experiments that Dr Hellstrom describes2 did not measure anatomic no-reflow as we have.3 No assessment of anatomic perfusion defect by either thioflavin S, carbon black, or other standard marker was used. Thus, it is not known whether short coronary occlusions could reverse the anatomic no-reflow phenomenon observed within a myocardial infarction. Areas of no-reflow in our infarct/reperfusion models are well-delineated subendocardial to midmyocardial perfusion defects associated with hemorrhage into the tissue, extensive capillary swelling, and blebbing. Much of the damage assessed by electron microscopy was in capillaries, which by definition cannot undergo spasm, as they do not have a smooth muscle cell layer. No-reflow may be multifactorial as suggested by Akasaka et al.4 Topol and Yadav5 have shown the contribution of atheroembolism to no-reflow in the setting of percutaneous coronary interventions. Development of catheters that can catch embolic debris seems to confirm this suggestion. Of course, it is possible that emboli may cause secondary spasm.
Thus, while we agree with Dr Hellstrom that spasm may be a contributing factor, we do not believe that it is the sole mechanism of no-reflow, at least in models of coronary occlusion/reperfusion resulting in substantial myocardial infarctions, which are the models we have studied.
References
- Rezkalla SH, Kloner RA. No-reflow phenomenon. Circulation. 2002; 105: 656–662.
[Free Full Text]
- Hellstrom HR. Coronary artery stasis after induced myocardial infarction in the dog. Cardiovasc Res. 1971; 5: 371–375.
[Abstract/Free Full Text]
- Kloner RA, Ganote CE, Jennings RB. The "no-reflow" phenomenon after temporary coronary occlusion in the dog. J Clin Invest. 1974; 54: 1496–1508.[Medline]
[Order article via Infotrieve]
- Akasaka T, Yoshida K, Kawamoto T, et al. Relation of phasic coronary flow velocity characteristics with TIMI perfusion grade and myocardial recovery after primary percutaneous transluminal coronary angioplasty and rescue stenting. Circulation. 2000; 101: 2361–2367.
[Abstract/Free Full Text]
- Topol EJ, Yadav JS. Recognition of the importance of embolization in atherosclerotic vascular disease. Circulation. 2000; 101: 570–580.
[Free Full Text]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||