What question did this study set out to answer?

To determine whether platelet-activating factor (PAF) and nitric oxide (NO) serve as downstream secondary mediators of tumor necrosis factor-alpha (TNF-alpha)-induced myocardial depression.

March 1, 1999Cardiovascular ResearchOpen Access

Role of nitric oxide and platelet-activating factor in cardiac alterations induced by tumor necrosis factor-α in the guinea-pig papillary muscle

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Population

Guinea pig papillary muscles

Comparison

Tumor necrosis factor-alpha 1-10 ng/ml, alone or… vs Controlled conditions (baseline)

Design

Preclinical

Authors

GAGiuseppe AlloattiAzienda Sanitaria Locale di Asti

Discussion

Member takes

Implication

Does not warrant clinical translation of TNF-alpha modulation; leaves open PAF-NO pathway as target in cytokine-mediated cardiac dysfunction.

Key Points

To determine whether platelet-activating factor (PAF) and nitric oxide (NO) serve as downstream secondary mediators of tumor necrosis factor-alpha (TNF-alpha)-induced myocardial depression.
Recorded isometric twitches and intracellular action potentials from isolated guinea pig papillary muscles exposed to TNF-alpha (1–10 ng/ml).
Tested mechanisms using endocardial endothelial disruption (0.5% Triton X-100), nitric oxide synthase inhibition (L-NAME vs. inactive D-NAME, 1 mM), and PAF-receptor antagonists (WEB 2170, 3 μM; CV 3988, 5 μM).
Quantified nitrite production via the Griess reagent assay and measured PAF production using a bioassay following cytokine stimulation.
TNF-alpha induced an initial transient positive inotropic phase followed by concentration-dependent decreases in myocardial contractility and action potential duration, an effect unaltered by endothelial destruction.
L-NAME, WEB 2170, and CV 3988 significantly prevented the electrical and mechanical depression induced by TNF-alpha and inhibited cytokine-stimulated nitrite accumulation.
TNF-alpha directly provoked PAF synthesis, and PAF challenge promoted nitrite production that was subsequently prevented by L-NAME pretreatment.

Structured PICO

Population

Guinea pig papillary muscles

Intervention

Tumor necrosis factor-alpha (TNF-alpha) 1-10 ng/ml, alone or with various inhibitors/antagonists (Triton X-100, L-NAME, D-NAME, WEB 2170, CV 3988, indomethacin, propranolol)

Comparator

Controlled conditions (baseline)

Outcome

Isometric twitches (contractility) and intracellular action potentialssurrogate

In guinea pig papillary muscles, the negative inotropic effects of TNF-alpha are mediated by the release of platelet-activating factor, which subsequently stimulates nitric oxide production.

Cite This Study

Giuseppe Alloatti (1999) studied this question.

synapsesocial.com/papers/6a853dc90b777c8ef0964858 https://doi.org/10.1016/s0008-6363(98)00250-8

Topics

Dual antiplatelet therapy

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Implication

Does not warrant clinical translation of TNF-alpha modulation; leaves open PAF-NO pathway as target in cytokine-mediated cardiac dysfunction.

Role of nitric oxide and platelet-activating factor in cardiac alterations induced by tumor necrosis factor-α in the guinea-pig papillary muscle

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Role of nitric oxide and platelet-activating factor in cardiac alterations induced by tumor necrosis factor-α in the guinea-pig papillary muscle

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

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