Effects of heparin in large doses on the extent of myocardial ischemia after acute coronary occlusion in the dog

Saliba, Michael J.; Covell, James W.; Bloor, Colin M.

doi:10.1016/0002-9149(76)90401-x

Cited by 51 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3 Significant difference, group 1 vs. group 3, p = 0.01. that heparin can be considered an immunosuppressive agent [15,16] . In cardiovascular surgery, heparin-coated extracorporeal circuits are widely used to block the complement cascade [17,18] . Numerous experimental ischemia-reperfusion models have shown that heparin doses in the 400-2,000 IU/kg range are protective in various tissues [15,19] .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Yuceturk

Yağmurdur²,

Gür

et al. 2007

Eur Surg Res

View full text Add to dashboard Cite

Objectives: The aim of this study was to investigate the effect of heparin on TNF-α and interleukin (IL)-6 levels and the complement system in liver regeneration in a murine model. Materials and Methods: 32 Wistar albino female rats weighing between 180 and 250 g were included in the study. The rats were divided into four groups as follows: group 1, treated with partial (50%) hepatectomy and intravenous heparin 1,000 IU/kg in repeated daily doses; group 2, treated with sham operation and intravenous heparin 1,000 IU/kg in repeated daily doses; group 3, treated with partial (50%) hepatectomy, and group 4 (controls), treated with only sham operation. Before the surgical intervention and after a general anesthetic had been administered to all rats, blood was taken from the left ventricle of each rat, and each sample was assessed to determine total complement hemolytic activity (CH₅₀/ml). On the 5th postoperative day, blood was taken to assess CH₅₀ activity and the levels of TNF-α and IL-6 via ELISA. Each rat was then killed by decapitation after which gravimetric analysis and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) were performed. Results: Serum CH₅₀ activity of group 1 was 4% as compared to 51% in group 3 (p = 0.01). The serum TNF-α level of group 1 was 43 pg/ml as compared to 86 pg/ml in group 3 (p = 0.002). The serum IL-6 level of group 1 was 19 pg/ml as compared to 44 pg/ml in group 3 (p = 0.02). The serum IL-6 level of group 2 was 4 pg/ml as compared to 44 pg/ml in group 3 (p = 0.005). According to the results of gravimetric analysis, the mean regeneration rate of group 1 was 4.4% as compared to 22% of group 3 (p = 0.001). The mean PCNA index values of group 2 was the highest of all groups (p = 0.01). However, the mean PCNA index value of group 1 was the lowest of all groups (p = 0.01). Conclusion: Because of its anti-inflammatory action via the complement system, heparin produced an unfavorable effect on liver regeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

“…This inhibitory action of heparin on C1 esterase means that heparin can be considered an immunosuppressive agent [17,18] . Also in a recent study it was shown that heparin reduces complement activation through alternative complement activation, probably at the C3 convertase level [29] .…”

Section: Discussionmentioning

confidence: 99%

Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Yuceturk

Yağmurdur²,

Gür

et al. 2007

Eur Surg Res

View full text Add to dashboard Cite

show abstract

“…Heparin (HEP) is an almost universal therapy for myocardial infarction to prevent coronary reocclusion and thromboembolic complications. For many years a second pharmacology of HEP, potentially protective against myocardial reperfusion injury, has been recognized at much higher doses than those used currently to produce anticoagulation (27). This effect of HEP is independent of its anticoagulant activity (2,8,18,19) and has been attributed to inhibition of the complement cascade (2,8).…”

mentioning

confidence: 99%

Nonanticoagulant heparin inhibits NF-κB activation and attenuates myocardial reperfusion injury

Thourani

Brar²,

Kennedy³

et al. 2000

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Heparin reduces ischemia-reperfusion injury to myocardium. This effect has been attributed to complement inhibition, but heparin also has other activities that might diminish ischemia-reperfusion. To further probe these mechanisms, we compared heparin or an o-desulfated nonanticoagulant heparin with greatly reduced anticomplement activity. When given at the time of coronary artery reperfusion in a canine model of myocardial infarction, heparin or o-desulfated heparin equally reduced neutrophil adherence to ischemic-reperfused coronary artery endothelium, influx of neutrophils into ischemic-reperfused myocardium, myocardial necrosis, and release of creatine kinase into plasma. Heparin or o-desulfated heparin also prevented dysfunction of endothelial-dependent coronary relaxation following ischemic injury. In addition, heparin and o-desulfated heparin inhibited translocation of the transcription nuclear factor-kappaB (NF-kappaB) from the cytoplasm to the nucleus in human endothelial cells and decreased NF-kappaB DNA binding in human endothelium and ischemic-reperfused rat myocardium. Thus heparin and nonanticoagulant heparin decrease ischemia-reperfusion injury by disrupting multiple levels of the inflammatory cascade, including the novel observation that heparins inhibit activation of the proinflammatory transcription factor NF-kappaB.

show abstract

“…Extremity tissue can withstand very long periods of ischemia, more than 24 hr of warm ischemia 35,36 and greater than 50 hr of cold ischemia. 37,38 The use of preischemic heparinization has yielded success in extending tolerance to ischemia in a variety of tissues, including brain, 39 heart, 40 kidney, 41 skin, 42 and muscle. 43,44 The idea of flushing or temporarily revascularizing an amputated part has been successfully applied clinically.…”

Section: Discussionmentioning

confidence: 99%

Brief ex vivo perfusion with heparinized and/or citrated whole blood enhances tolerance of free muscle flaps to prolonged ischemia

Fowler

Cooley

1999

Microsurgery

View full text Add to dashboard Cite

This study investigated the use of heparinized and/or citrated whole blood as a perfusate for enhancing muscle tolerance to warm ischemia. Unilateral cutaneous trunci muscle flaps were harvested from Sprague-Dawley rats and stored for 10 hr at 22-24 degrees C prior to transplantation to the groin. One group served as a non-perfused control. In three experimental groups, the flaps were hand-perfused ex vivo with 1.0 ml of heparinized, citrated, or heparinized and citrated autogenous whole blood at physiological pressures. Perfusion was administered over a 10-min period 5 hr into the ischemic period. Flaps were revascularized on the femoral vessels and then harvested 48 hr following revascularization. Tissue injury was assessed by calculation of flap weight change (indicator of tissue edema), histochemical evaluation of muscle dehydrogenase activity (nitroblue tetrazolium assay), and light microscopy. All perfused groups had significantly higher muscle dehydrogenase activity compared with non-perfused controls (P < 0.005). Perfusion with combined heparin-citrated blood was significantly more protective than perfusion with either anticoagulant alone (P < 0.025). The only statistically significant reduction in percent flap edema was seen in the combined heparin-citrate perfusion of flaps compared with nonperfused controls (P < 0.05). Histologic evaluation confirmed a reduction in tissue edema in the perfused flaps. We conclude that mid-ischemic perfusion with heparinized and/or citrated blood limits the deleterious effects of extended warm ischemia.

show abstract

Effects of heparin in large doses on the extent of myocardial ischemia after acute coronary occlusion in the dog

Cited by 51 publications

References 33 publications

Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Nonanticoagulant heparin inhibits NF-κB activation and attenuates myocardial reperfusion injury

Brief ex vivo perfusion with heparinized and/or citrated whole blood enhances tolerance of free muscle flaps to prolonged ischemia

Contact Info

Product

Resources

About