Is the tumour necrosis factor-alpha response following resuscitation gender dependent in the swine model?

Niemann, James T.; Rosborough, John P.; Youngquist, Scott T.

doi:10.1016/j.resuscitation.2007.11.022

Cited by 24 publications

(12 citation statements)

References 29 publications

(6 reference statements)

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“…We used only male swine in this study due to prior observations suggesting that there are gender differences in the proinflammatory response following resuscitation and that the response is more dramatic and more predictable in males than females. (28) We evaluated one cardiac arrest duration (7 min) prior initiation of resuscitation efforts. A long duration of ischemia may have resulted in a more pronounced inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Infliximab attenuates early myocardial dysfunction after resuscitation in a swine cardiac arrest model

Niemann

Youngquist

Rosborough

et al. 2010

Critical Care Medicine

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Objective Left ventricular (LV) dysfunction after successful cardiopulmonary resuscitation contributes to early death following resuscitation. Proinflammatory cytokines are known to depress myocardial function and TNF-alpha has been shown to increase after successful resuscitation. We hypothesized that blocking the effects of TNF-alpha with infliximab would prevent or minimize postresuscitation cardiac dysfunction. Design Randomized, placebo-controlled comparative study. Setting Large animal research laboratory. Subjects Twenty-eight anesthetized and instrumented domestic male swine (Yorkshire and Yorkshire/Hampshire mix, weight 35-45 kg). Interventions Infusion of infliximab (5 mg/kg) or normal saline after resuscitation from VF cardiac arrest. Measurements and Main Results Hemodynamic variables, indices of LV function, and TNF-alpha were measured before and after 8 min of cardiac arrest during the early post-resuscitation period (3 hrs). Within 5 min of restoration of spontaneous circulation, 14 animals received infliximab, 5 mg/kg, infused over 30 min. Fourteen animals received an infusion of normal saline. Inotropes and vasopressors were not administered to either group following resuscitation. TNF-alpha increased following restoration of circulation and remained elevated throughout the observation period. Differences between groups were not significant. IL-1β concentration did not change significantly during the observation period in either study group. Mean arterial pressure and stroke work were significantly greater in the infliximab group within 30 mins of resuscitation and these differences were sustained throughout the 3 hr postresuscitation period. The effect of TNF-α blockade was evident only in animals with a significant increase (doubling) in plasma TNF-α at 30 minutes post-arrest. Conclusion TNF-α plays a role in post-arrest cardiac dysfunction and Infliximab may attenuate or prevent postresuscitation myocardial dysfunction when given immediately after resuscitation.

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Section: Discussionmentioning

confidence: 99%

Infliximab attenuates early myocardial dysfunction after resuscitation in a swine cardiac arrest model

Niemann

Youngquist

Rosborough

et al. 2010

Critical Care Medicine

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“…We used only male swine because previous work has demonstrated that the post-resuscitation inflammatory response in males is more robust than that observed in female swine of similar age. 21 The anesthetics used in this study may affected pre-arrest and post-resuscitation cardiac function and possibly the innate inflammatory response. 23 However, the anesthetic regimen was the same for the two treatment groups.…”

Section: Discussionmentioning

confidence: 99%

“…There is also evidence that a systemic inflammatory response follows resuscitation and is characterized by an increase in circulating inflammatory cytokines. 13,13,21 Cytokines, particularly TNF-α, are known to cause myocardial depression by altering calcium homeostasis in myocytes. 22 …”

Section: Discussionmentioning

confidence: 99%

TNF-α blockade improves early post-resuscitation survival and hemodynamics in a swine model of ischemic ventricular fibrillation

Niemann¹,

Youngquist²,

Shah³

et al. 2013

Resuscitation

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Aim of the study Inflammatory cytokines have been implicated in the pathophysiology of post cardiac arrest syndrome, including myocardial dysfunction and hypotension, often leading to multi-organ system dysfunction and death. We hypothesized that administration of infliximab after return of spontaneous circulation (ROSC) would ameliorate hypotension and myocardial dysfunction and prolong survival. Methods Domestic swine were anesthetized and instrumented. Balloon occlusion of the LAD coronary artery just distal to the first septal perforator was performed and VF followed spontaneously in all animals. After 7 min,, chest compressions, defibrillation, and standard ACLS resuscitation was performed. Animals achieving ROSC (N=32) were randomized to receive infliximab (5 mg/kg, n=16) or vehicle (250 mL normal saline, n=16) immediately post-ROSC and survival and hemodynamics were monitored for 3 hours. Results There were no differences in prearrest hemodynamic variables, TNF-α levels, or resuscitation variables between groups. Both groups demonstrated a time dependent decline in mean arterial pressure (MAP) and stroke work (SW) post-ROSC with a nadir at 1 hour followed by recovery over hours 2 and 3. This decline was blunted in infliximab-treated swine (1-hour between group difference in MAP 21 mmHg, 95% CI 3–38 mmHg and SW 6.7 gm-m, 95% CI 0.4–13 at 1 hour). Left ventricular systolic dp/dt fell in the vehicle group (-437 mm Hg/sec, 95% CI -183 to -690) but did not in the infliximab group. Tau rose only in the vehicle group (44 msec, 95% CI 1–87). Short-term survival was higher in the infliximab group (Kaplan-Meier p = 0.022). Conclusions Blockade of TNF-α in the immediate post-ROSC period improved survival and hemodynamic parameters in this swine model of ischemic VF.

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“…25 Male swine were employed in this study due to gender differences in the cytokine response to cardiac arrest observed in this species. 26 It is uncertain whether similar differences exist in human populations. We did not induce hypothermia during the early post-arrest period modeled in this investigation.…”

Section: Discussionmentioning

confidence: 99%

A comparison of etanercept vs. infliximab for the treatment of post-arrest myocardial dysfunction in a swine model of ventricular fibrillation

et al. 2013

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Aims To compare the effects of two TNF-α antagonists, etanercept and infliximab, on post-cardiac arrest haemodynamics and global left ventricular function (LV) in a swine model following ventricular fibrillation (VF). Methods Domestic swine (n=30) were placed under general anaesthesia and instrumented before VF was induced electrically. After 7 minutes of VF, standard ACLS resuscitation was performed. Animals achieving return of spontaneous circulation (ROSC) were randomized to immediately receive infliximab (5 mg/kg, n=10) or etanercept (0.3 mg/kg [4 mg/m2], n=10) or vehicle (250 mL normal saline [NS], n=10) and LV function and haemodynamics were monitored for 3 hours. Results Following ROSC, mean arterial pressure (MAP), stroke work (SW), and LV dP/dt fell from prearrest values in all groups. However, at the 30 minute nadir, infliximab-treated animals had higher MAP than either the NS group (difference 14.4 mm Hg, 95% confidence interval [CI] 4.2–24.7) or the etanercept group (19.2 mm Hg, 95% CI 9.0–29.5), higher SW than the NS group (10.3 gm-m, 95% CI 5.1–15.5) or the etanercept group (8.9 gm-m, 95% CI 4.0–14.4) and greater LV dP/dt than the NS group (282.9 mm Hg/sec, 95% CI 169.6–386.1 higher with infliximab) or the etanercep group (228.9 mm Hg/sec, 95% CI 115.6–342.2 higher with infliximab). Conclusions Only infliximab demonstrated a beneficial effect on post cardiac arrest haemodynamics and LV function in this swine model. Etanercept was no better in this regard than saline.

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Is the tumour necrosis factor-alpha response following resuscitation gender dependent in the swine model?

Cited by 24 publications

References 29 publications

Infliximab attenuates early myocardial dysfunction after resuscitation in a swine cardiac arrest model

Infliximab attenuates early myocardial dysfunction after resuscitation in a swine cardiac arrest model

TNF-α blockade improves early post-resuscitation survival and hemodynamics in a swine model of ischemic ventricular fibrillation

A comparison of etanercept vs. infliximab for the treatment of post-arrest myocardial dysfunction in a swine model of ventricular fibrillation

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