Time‐ and dose‐related regional fluxes of tissue‐type plasminogen activator in anesthetized endotoxemic pigs

Nyberg, Annette; Jakob, Stephan M.; Seeman-Lodding, H.; Porta, Francesca; Bracht, Hendrik; Bischofberger, H; Jern, Christina; Takala, Jukka; Åneman, Anders

doi:10.1111/j.1399-6576.2007.01481.x

Cited by 2 publications

(2 citation statements)

References 22 publications

(23 reference statements)

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“…In addition, ac ross-species comparison of the proteolytic activity of plasmin activated by the staphylokinaseh as shownt hatt here arem ajors imilarities betweenh umans andp igs (37).H owever,a ni n-vitros tudyh as shownd ecreased sensitivity of porcine plasminogen to human tissueplasminogen activator (11).Thus,our findings confirmthe potential usefulness of pig as an experimentalanimal species for examining the fibrinolyticpathway (38)(39)(40)(41)(42)(43). Previousexamples include studiese xamining the effects of plasminogen activators forp revention of the adult respiratoryd istresss yndrome ( 39), urokinase in adisseminated intravascular coagulation model (40) andstudies on tissue-type plasminogen activator (41,42).…”

Section: Similaritiesbetween Human and Pigsupporting

confidence: 73%

Interspecies differences in coagulation profile

Siller‐Matula¹,

Plasenzotti²,

Spiel³

et al. 2008

Thromb Haemost

185

121

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Many animals are used in research on blood coagulation and fibrinolysis, but the relevance of animal models to human health is often questioned because of differences between species. The objective was to find an appropriate animal species, which mimics the coagulation profile in humans most adequately. Species differences in the coagulation profile with and without thrombin stimulation in vitro were assessed in whole blood by Rotation Thromboelastometry (ROTEM). Endogenous thrombin generation was measured in platelet-poor plasma. Measurements were performed in blood from five different species: humans, rats, pigs, sheep and rabbits. In humans and sheep, the clotting time (ROTEM) was in the same range with or without thrombin stimulation and a 100-fold lower dose of thrombin (0.002 IU) was required to cause a shortening in the clotting time as compared to rats, pigs and rabbits (0.2 IU) (p<0.05). Similarly, the endogenous thrombin potential (ETP) was in the same range in humans and sheep. The maximum clot firmness with or without thrombin stimulation was similar in rabbits and humans. The maximum lysis with or without thrombin stimulation was similar in humans and pigs. Significant species differences exist in the coagulation profile with or without thrombin stimulation. Most importantly, sheep had a clotting time most similar to humans and could thus be a suitable species for translational coagulation studies. Moreover, our findings confirm the potential usefulness of pigs as an experimental species to study fibrinolytic pathway and support the usefulness of rabbits as a species for examining platelets.

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Section: Similaritiesbetween Human and Pigsupporting

confidence: 73%

Interspecies differences in coagulation profile

Siller‐Matula¹,

Plasenzotti²,

Spiel³

et al. 2008

Thromb Haemost

185

121

View full text Add to dashboard Cite

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“…Some of the data obtained during the 18 h of endotoxin infusion, prior to dobutamine exposure, have been published previously (6,29,30). CO values of some of the animals have been published in another study where thermodilution was compared with esophageal Doppler (38).…”

Section: Methodsmentioning

confidence: 99%

Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia

Jakob¹,

Bracht²,

Porta³

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Takala J. Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia. Am J Physiol Gastrointest Liver Physiol 303: G247-G255, 2012. First published May 3, 2012 doi:10.1152/ajpgi.00433.2011.-Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle (n ϭ 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 g/kg per minute or another vehicle (n ϭ 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/ flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 Ϯ 11 mmHg vs. 58 Ϯ 8 mmHg (mean Ϯ SD); P ϭ 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18 -1.32) mmHg/ml vs. 0.22 (0.08 -0.60) mmHg/ml; P ϭ 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia (P ϭ 0.031; constriction-timegroup interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22-134%) in controls vs. 53% (37-85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12-47%) of baseline (P ϭ 0.043) vs. 17% (Ϫ7-32%) in endotoxemia (P ϭ 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR. hepatic arterial buffer response; sepsis; liver INADEQUATE SPLANCHNIC PERFUSION is associated with multiple organ failure and death (11, 23), especially when hepatic dysfunction is present (28). Global hepatic blood flow is supposed to be relatively protected when gut blood flow decreases because hepatic arterial flow increases when portal venous flow decreases (the hepatic arterial buffer response, HABR) (25, 26). However, evidence suggests that the HABR is diminished or even abolished during endotoxemia (1) and when gut blood flow becomes very low (19,31).The HABR is usually assessed by decreasing superior mesenteric or portal venous blood flow and measurement of ...

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Time‐ and dose‐related regional fluxes of tissue‐type plasminogen activator in anesthetized endotoxemic pigs

Abstract: Endotoxemia induces an early increase in mesenteric tPA release and hepatic tPA uptake related to the severity of endotoxemia. The time patterns of changes in mesenteric and hepatic tPA fluxes are similar in acute high-dose endotoxemia and sustained low-dose endotoxemia.

Cited by 2 publications

References 22 publications

Interspecies differences in coagulation profile

Interspecies differences in coagulation profile

Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia

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