Pentoxifylline reduces leukocyte retention in the coronary microcirculation early in reperfusion following ischemia

Leslie S Ritter, D. S. Wilson, S. K. Williams, J. G. Copeland, P. F. McDonagh

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Using direct visualization techniques, we recently confirmed earlier histologic studies that leukocytes accumulate primarily in the coronary capillaries of ischemic hearts during early reperfusion. The purpose of this study was to determine if pentoxifylline (PTX) would reduce leukocyte trapping in post-ischemic hearts. Isolated rat hearts were subjected to 30 min of 37°C, no-flow ischemia. Hearts were initially reperfused with diluted whole blood containing fluorescent leukocytes. At 5, (R5), 20, and 35 min of reperfusion, the deposition of leukocytes in the coronary capillaries and venules was observed directly using intravital fluorescence microscopy. Three groups were studied: a non-ischemic control group (group I) and postischemic groups reperfused with diluted whole blood treated with vehicle group II or PTX (5 mM; group III). Postischemic reperfusion with unactivated blood caused a significant trapping of leukocytes in coronary capillaries throughout reperfusion (R5, group I = 2.0 ± 0.3 vs. group II = 5.7 ± 0.6 leukocytes/capillary field, p < 0.05). The addition of PTX reduced capillary leukocyte trapping below control values throughout reperfusion (R5, group III = 1.6 ± 0.2 leukocytes/capillary field, p < 0.05). At R5, there was no statistically significant difference in leukocyte accumulation in venules for all groups (group I = 1.5 ± 0.6, group II = 3.2 ± 0.4, group III = 3.3 ± 0.4 leukocytes/100 μm venule). During the reperfusion period, leukocyte persistence in the capillaries of postischemic hearts (36%) was greater than in the venules (13%). These data indicate that early in reperfusion after myocardial ischemia, leukocyte trapping occurs primarily in the coronary capillaries. PTX reduced early leukocyte trapping in the capillaries. The results also demonstrate that during reperfusion, the mechanisms affecting capillary retention are more persistent than those in the venule. These findings suggest that attempts to attenuate the damaging potential of early leukostasis in capillaries consider the biophysical properties of the leukocyte.

Original languageEnglish (US)
Pages (from-to)170-179
Number of pages10
JournalInternational journal of microcirculation, clinical and experimental / sponsored by the European Society for Microcirculation
Volume16
Issue number4
StatePublished - Jul 1996

Fingerprint

Pentoxifylline
Microcirculation
Reperfusion
Leukocytes
Ischemia
Venules
Leukostasis
Fluorescence Microscopy
Myocardial Ischemia

Keywords

  • Coronary microcirculation
  • Ischemia-reperfusion
  • Leukocytes
  • Pentoxifylline
  • Rat
  • Reperfusion injury

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

Cite this

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title = "Pentoxifylline reduces leukocyte retention in the coronary microcirculation early in reperfusion following ischemia",
abstract = "Using direct visualization techniques, we recently confirmed earlier histologic studies that leukocytes accumulate primarily in the coronary capillaries of ischemic hearts during early reperfusion. The purpose of this study was to determine if pentoxifylline (PTX) would reduce leukocyte trapping in post-ischemic hearts. Isolated rat hearts were subjected to 30 min of 37°C, no-flow ischemia. Hearts were initially reperfused with diluted whole blood containing fluorescent leukocytes. At 5, (R5), 20, and 35 min of reperfusion, the deposition of leukocytes in the coronary capillaries and venules was observed directly using intravital fluorescence microscopy. Three groups were studied: a non-ischemic control group (group I) and postischemic groups reperfused with diluted whole blood treated with vehicle group II or PTX (5 mM; group III). Postischemic reperfusion with unactivated blood caused a significant trapping of leukocytes in coronary capillaries throughout reperfusion (R5, group I = 2.0 ± 0.3 vs. group II = 5.7 ± 0.6 leukocytes/capillary field, p < 0.05). The addition of PTX reduced capillary leukocyte trapping below control values throughout reperfusion (R5, group III = 1.6 ± 0.2 leukocytes/capillary field, p < 0.05). At R5, there was no statistically significant difference in leukocyte accumulation in venules for all groups (group I = 1.5 ± 0.6, group II = 3.2 ± 0.4, group III = 3.3 ± 0.4 leukocytes/100 μm venule). During the reperfusion period, leukocyte persistence in the capillaries of postischemic hearts (36{\%}) was greater than in the venules (13{\%}). These data indicate that early in reperfusion after myocardial ischemia, leukocyte trapping occurs primarily in the coronary capillaries. PTX reduced early leukocyte trapping in the capillaries. The results also demonstrate that during reperfusion, the mechanisms affecting capillary retention are more persistent than those in the venule. These findings suggest that attempts to attenuate the damaging potential of early leukostasis in capillaries consider the biophysical properties of the leukocyte.",
keywords = "Coronary microcirculation, Ischemia-reperfusion, Leukocytes, Pentoxifylline, Rat, Reperfusion injury",
author = "Ritter, {Leslie S} and Wilson, {D. S.} and Williams, {S. K.} and Copeland, {J. G.} and McDonagh, {P. F.}",
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T1 - Pentoxifylline reduces leukocyte retention in the coronary microcirculation early in reperfusion following ischemia

AU - Ritter, Leslie S

AU - Wilson, D. S.

AU - Williams, S. K.

AU - Copeland, J. G.

AU - McDonagh, P. F.

PY - 1996/7

Y1 - 1996/7

N2 - Using direct visualization techniques, we recently confirmed earlier histologic studies that leukocytes accumulate primarily in the coronary capillaries of ischemic hearts during early reperfusion. The purpose of this study was to determine if pentoxifylline (PTX) would reduce leukocyte trapping in post-ischemic hearts. Isolated rat hearts were subjected to 30 min of 37°C, no-flow ischemia. Hearts were initially reperfused with diluted whole blood containing fluorescent leukocytes. At 5, (R5), 20, and 35 min of reperfusion, the deposition of leukocytes in the coronary capillaries and venules was observed directly using intravital fluorescence microscopy. Three groups were studied: a non-ischemic control group (group I) and postischemic groups reperfused with diluted whole blood treated with vehicle group II or PTX (5 mM; group III). Postischemic reperfusion with unactivated blood caused a significant trapping of leukocytes in coronary capillaries throughout reperfusion (R5, group I = 2.0 ± 0.3 vs. group II = 5.7 ± 0.6 leukocytes/capillary field, p < 0.05). The addition of PTX reduced capillary leukocyte trapping below control values throughout reperfusion (R5, group III = 1.6 ± 0.2 leukocytes/capillary field, p < 0.05). At R5, there was no statistically significant difference in leukocyte accumulation in venules for all groups (group I = 1.5 ± 0.6, group II = 3.2 ± 0.4, group III = 3.3 ± 0.4 leukocytes/100 μm venule). During the reperfusion period, leukocyte persistence in the capillaries of postischemic hearts (36%) was greater than in the venules (13%). These data indicate that early in reperfusion after myocardial ischemia, leukocyte trapping occurs primarily in the coronary capillaries. PTX reduced early leukocyte trapping in the capillaries. The results also demonstrate that during reperfusion, the mechanisms affecting capillary retention are more persistent than those in the venule. These findings suggest that attempts to attenuate the damaging potential of early leukostasis in capillaries consider the biophysical properties of the leukocyte.

AB - Using direct visualization techniques, we recently confirmed earlier histologic studies that leukocytes accumulate primarily in the coronary capillaries of ischemic hearts during early reperfusion. The purpose of this study was to determine if pentoxifylline (PTX) would reduce leukocyte trapping in post-ischemic hearts. Isolated rat hearts were subjected to 30 min of 37°C, no-flow ischemia. Hearts were initially reperfused with diluted whole blood containing fluorescent leukocytes. At 5, (R5), 20, and 35 min of reperfusion, the deposition of leukocytes in the coronary capillaries and venules was observed directly using intravital fluorescence microscopy. Three groups were studied: a non-ischemic control group (group I) and postischemic groups reperfused with diluted whole blood treated with vehicle group II or PTX (5 mM; group III). Postischemic reperfusion with unactivated blood caused a significant trapping of leukocytes in coronary capillaries throughout reperfusion (R5, group I = 2.0 ± 0.3 vs. group II = 5.7 ± 0.6 leukocytes/capillary field, p < 0.05). The addition of PTX reduced capillary leukocyte trapping below control values throughout reperfusion (R5, group III = 1.6 ± 0.2 leukocytes/capillary field, p < 0.05). At R5, there was no statistically significant difference in leukocyte accumulation in venules for all groups (group I = 1.5 ± 0.6, group II = 3.2 ± 0.4, group III = 3.3 ± 0.4 leukocytes/100 μm venule). During the reperfusion period, leukocyte persistence in the capillaries of postischemic hearts (36%) was greater than in the venules (13%). These data indicate that early in reperfusion after myocardial ischemia, leukocyte trapping occurs primarily in the coronary capillaries. PTX reduced early leukocyte trapping in the capillaries. The results also demonstrate that during reperfusion, the mechanisms affecting capillary retention are more persistent than those in the venule. These findings suggest that attempts to attenuate the damaging potential of early leukostasis in capillaries consider the biophysical properties of the leukocyte.

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KW - Ischemia-reperfusion

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KW - Pentoxifylline

KW - Rat

KW - Reperfusion injury

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