Microvascular compression during myocardial ischemia: mechanistic basis for no-reflow phenomenon

Manciet, L H; Poole, D. C.; McDonagh, Paul F.; Copeland, Jack G.; Mathieu-Costello, Odile

doi:10.1152/ajpheart.1994.266.4.h1541

Cited by 68 publications

(53 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In relation to post-ischaemic reflow, it has been suggested that microvascular compression is the major determinant of postischaemic coronary flow (Nevalainen et al 1986;Manciet et al 1994). The unloaded and isovolumically contracting hearts presented an interesting opportunity to test this notion.…”

Section: Responses To Ischaemia-reperfusion: Isovolumic Contraction Vmentioning

confidence: 99%

Functional properties and responses to ischaemia‐reperfusion in Langendorff perfused mouse heart

Headrick¹,

Peart²,

Hack³

et al. 2001

Experimental Physiology

112

View full text Add to dashboard Cite

Despite minimal model characterisation Langendorff perfused murine hearts are increasingly employed in cardiovascular research, and particularly in studies of myocardial ischaemia and reperfusion. Reported contractility remains poor and ischaemic recoveries variable. We characterised function in C57/BL6 mouse hearts using a ventricular balloon or apicobasal displacement and assessed responses to 10-30 min global ischaemia. We examined the functional effects of pacing, ventricular balloon design, perfusate filtration, [Ca"] and temperature. Contractility was high in isovolumically functioning mouse hearts (measured as the change in pressure with time (+dP/dt), 6000-7000 mmHg s-I) and was optimal at a heart rate of -420 beats min-', with the vasculature sub-maximally dilated, and the cellular energy state high. Post-ischaemic recovery (after 40 min reperfusion) was related to the ischaemic duration: developed pressure recovered by 82 f YO, 73 f 4u/, 68 f 3%, 57 f 2% and 41 f 5% after 10, 15, 20, 25 and 30 min ischaemia, respectively. Ventricular compliance and elastance were both reduced post-ischaemia. Post-ischaemic recoveries were lower in the apicobasal model (80 +-4 YO, 58 k 7 YO, 40 +-3 %, 32 +-7 % and 25 2 5 YO) despite greater reflow and lower metabolic rate (pre-ischaemic myocardial O2 consumption (Vo2,,,,) 127 f 15 vs. 198 k 17 p l O2 min-' g-'), contracture, enzyme and purine efflux. Electrical pacing slowed recovery in both models, small ventricular balloons (unpressurised volumes C 50-60 p1) artificially depressed ventricular function and recovery from ischaemia, and failure to filter the perfusion fluid to C 0.45 pm depressed pre-and post-ischaemic function. With attention to these various experimental factors, the buffer perfused isovolumically contracting mouse heart is shown to be stable and highly energised, and to possess a high level of contractility, The isovolumic model is more reliable in assessing ischaemic responses than the commonly employed apicobasal model. Experimental Physiology (200 1) 86.6, 703-7 16.

show abstract

Section: Responses To Ischaemia-reperfusion: Isovolumic Contraction Vmentioning

confidence: 99%

Functional properties and responses to ischaemia‐reperfusion in Langendorff perfused mouse heart

Headrick¹,

Peart²,

Hack³

et al. 2001

Experimental Physiology

112

View full text Add to dashboard Cite

show abstract

“…During reperfusion, accumulation of leukocytes in the microvasculature that leads to mechanical plugging (1,7,8) and interactions with platelets, the endothelium, and cardiomyocytes has been put forward to explain the progression of anatomic no reflow. In addition, tissue edema (27) and oxygen free radicals (6) derived from polymorphonuclear cells, the xanthine oxidase reaction, or mitochondria may be involved in reperfusion-related expansion of anatomic no reflow (34) and hence contribute to the size of perfusion defects after 3 h of reperfusion. Accordingly, the irreversible damage of cardiomyocytes could initiate a chain reaction and serve as the inflammatory stimulus that leads to leukocyte accumulation, oxygen free radical production, tissue edema, and, subsequently, microvascular perfusion defects with the observed close accordance in size and spatial distribution of no reflow and necrosis.…”

Section: Microvascular and Myocardial Damage In Reperfused Infarctsmentioning

confidence: 99%

Is microvascular protection by cariporide and ischemic preconditioning causally linked to myocardial salvage?

Reffelmann

Kloner

2003

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Two independent cardioprotective interventions, Na+/H+ exchange inhibition and ischemic preconditioning (PC), were investigated with respect to differential effects on microvascular and myocardial salvage in anesthetized rabbits (30 min of ischemia, 180 min of reperfusion). Cariporide (Car, 300 μg/kg) administered before occlusion and PC reduced infarct size (IS) as measured by triphenyltetrazolium staining [control, 46.0 ± 4.2% of risk area (RA); Car, 17.6 ± 3.7% ( P< 0.01); PC, 27.5 ± 4.1% ( P < 0.01)] and concomitantly decreased the area of anatomic no reflow (ANR) as measured by thioflavin S staining [control, 40.4 ± 3.7%; Car, 19.0 ± 2.9% ( P < 0.01); PC, 26.9 ± 3.4% ( P < 0.05)]. Regional myocardial blood flow (RMBF, measured by radioactive microspheres) in the RA, which deteriorated between 30 and 180 min of reperfusion (control, from 79 ± 6 to 26 ± 2% of nonischemic flow), was shifted to higher values with both treatments [Car, from 110 ± 12 to 49 ± 7% ( P < 0.05); PC, from 109 ± 8 to 38 ± 6% ( P < 0.05)]. However, neither intervention uncoupled the close relationship between IS and ANR ( r= 0.92–0.95) or RMBF. Car given at reperfusion did not alter IS, ANR, RMBF, or the close interrelationships. Because size and spatial distribution of no reflow and myocardial necrosis remained closely coupled with independent cardioprotective interventions, a potential causal connection between microvascular and myocardial salvage is discussed.

show abstract

“…Several mechanisms can initiate no-reflow in previously ischemic myocardium: (a) embolization of particulate atherosclerotic debris from the culprit lesion into the coronary microcirculation, both after mechanical or thrombolytic reopening of epicardial coronary arteries [9]; (b) platelet and platelet/leukocyte aggregates which are either released from the culprit lesion or form in the microcirculation [2]; (c) intense vasoconstriction in response to soluble factors (endothelin, serotonin, thromboxane) which are released from the culprit lesion [12]; (d) extravascular compression of the capillary bed by edema of the surrounding myocardium and interstitium [15]; and (e) edema and physical disintegration of the capillary vascular structures per se [13]. These pathomechanisms are not mutually exclusive, and their contribution to the no-reflow phenomenon may vary temporally and spatially as well as between different experimental models and individual patients.…”

mentioning

confidence: 99%

Myocardial infarction and coronary microvascular obstruction: an intimate, but complicated relationship

2013

View full text Add to dashboard Cite

Timely reperfusion is the only way to rescue ischemic myocardium from impending infarction. However, reperfusion also adds a component of injury to that incurred during ischemia and thus contributes to final infarct size [6,20,28]. It appears that all conditioning strategies which delay infarct size development and/or reduce infarct size act through attenuation of such reperfusion injury [7]. Apart from its contribution to cardiomyocyte necrosis, reperfusion is frequently also characterized by the development of areas of no-reflow within the previously ischemic myocardium [10]. Evidence for microvascular no-reflow by angiography or MRI despite successfully reopened epicardial coronary arteries in patients with myocardial infarction is associated with impaired recovery of ventricular function and worse survival [19].The coexistence of infarcted cardiomyocytes and areas of coronary microvascular no-reflow in reperfused myocardium is well established [13]; however the underlying mechanisms are not really clear. Several mechanisms can initiate no-reflow in previously ischemic myocardium: (a) embolization of particulate atherosclerotic debris from the culprit lesion into the coronary microcirculation, both after mechanical or thrombolytic reopening of epicardial coronary arteries The analysis of temporal and spatial relationships between infarcted myocardium and no-reflow is largely limited by methodological restraints. By definition, infarcted myocardium and no-reflow are confined to the previously ischemic area at risk. This appears trivial, but when analyzed by clinical imaging technology, the area at risk is often not determined or not clear. Slow/no-flow phenomena outside the area at risk may also occur but have a different underlying pathophysiology, e.g., reflex-mediated coronary vasoconstriction [4,8]. Myocardial infarction develops progressively during ischemia, and a separate component of irreversible injury is added during early reperfusion; the relative contribution of infarction which develops during ischemia and during reperfusion varies and depends on the duration of ischemia [3]. Even with gold standard technology (TTC staining) in the experiment, infarcted tissue is only recognized as such after several hours of reperfusion, and no distinction between myocardium infarcting during ischemia and during reperfusion is possible. No-reflow, as evidenced by lack of endothelial staining by thioflavin in the experiment [13], develops rapidly during early reperfusion and progresses over time [1,22,23]. Most studies indicate that no-reflow areas are This comment refers to the article available at

show abstract

Microvascular compression during myocardial ischemia: mechanistic basis for no-reflow phenomenon

Cited by 68 publications

References 0 publications

Functional properties and responses to ischaemia‐reperfusion in Langendorff perfused mouse heart

Functional properties and responses to ischaemia‐reperfusion in Langendorff perfused mouse heart

Is microvascular protection by cariporide and ischemic preconditioning causally linked to myocardial salvage?

Myocardial infarction and coronary microvascular obstruction: an intimate, but complicated relationship

Contact Info

Product

Resources

About