Anaphylaxis in the monkey: hemodynamics and blood flow distribution

Smedegård, G.; Revenäs, Björn; Arfors, Karl-E.

doi:10.1111/j.1748-1716.1979.tb06389.x

Cited by 34 publications

(12 citation statements)

References 20 publications

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“…Immune complexes cause thrombocytopenia in primates by cross-linking of FcgRIIa on the platelet surface, resulting in activation. Platelet activation can result in pulmonary thromboemboli, complement activation, and release of vasoactive amines that cause pulmonary venoconstriction (Del Conde et al 2005;Hedin and Smedegard 1979;Radegran, Drugge, and Olsson 1974;Radegran and McAslan 1972;Revenas, Smedegard, and Saldeen 1980;Smedegard, Revenas, and Arfors 1979).…”

Section: Hypersensitivity Reactionsmentioning

confidence: 99%

Unexpected Hematologic Effects of Biotherapeutics in Nonclinical Species and in Humans

Everds

Tarrant²

2013

Toxicol Pathol

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Biotherapeutics are expanding the arsenal of therapeutics available for treating and preventing disease. Although initially thought to have limited side effects due to the specificity of their binding, these drugs have now been shown to have potential for adverse drug reactions including effects on peripheral blood cell counts or function. Hematotoxicity caused by a biotherapeutic can be directly related to the activity of the biotherapeutic or can be indirect and due to autoimmunity, biological cascades, antidrug antibodies, or other immune system responses. Biotherapeutics can cause hematotoxicity primarily as a result of cellular activation, cytotoxicity, drug-dependent and independent immune responses, and sequelae from initiating cytokine and complement cascades. The underlying pathogenesis of biotherapeutic-induced hematotoxicity often is poorly understood. Nonclinical studies have generally predicted clinical hematotoxicity for recombinant cytokines and growth factors. However, most hematologic liabilities of biotherapeutics are not based on drug class but are species specific, immune-mediated, and of low incidence. Despite the potential for unexpected hematologic toxicity, the risk-benefit profile of most biotherapeutics is favorable; hematologic effects are readily monitorable and managed by dose modification, drug withdrawal, and/or therapeutic intervention. This article reviews examples of biotherapeutics that have unexpected hematotoxicity in nonclinical or clinical studies.

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Section: Hypersensitivity Reactionsmentioning

confidence: 99%

Unexpected Hematologic Effects of Biotherapeutics in Nonclinical Species and in Humans

Everds

Tarrant²

2013

Toxicol Pathol

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“…Their studies, however, focused on functional changes of respiratory and hemodynamic parameters associated with anaphylactic shock, and detailed descriptions of blood flow distribution are lacking. In contrast, Smedegard et al extensively examined anaphylaxis-induced alterations in hemodynamics and blood flow distribution in a monkey model (25,26). They demonstrated that animals developed a severe state of shock within two minutes following the antigen challenge, with high pulmonary vascular resistance, low cardiac output, and profound hypotension.…”

Section: Discussionmentioning

confidence: 86%

Urinary Trypsin Inhibitor Improves Peripheral Microcirculation and Bronchospasm Associated with Systemic Anaphylaxis in Rabbits In Vivo

Komori¹,

Takada²,

Tomizawa

et al. 2003

Shock

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Using intravital microscopy of the rabbit ear for quantitative studies of microvascular dynamics, we examined the impact of urinary trypsin inhibitor (UTI), a proteolytic enzyme inhibitor, on microvascular changes during immune complex-mediated anaphylaxis. A total of 50 rabbits, previously sensitized with horse serum, were anesthetized and mechanically ventilated with pentobarbital and isoflurane for the intravital microscopy. Rabbits were then challenged with intravenous injection of horse serum to induce systemic anaphylaxis. One minute after the challenge, each rabbit was randomly assigned to receive saline (group C), 50,000 units x kg(-1) of UTI (group U1), or 150,000 units x kg(-1) (group U2). There were no statistical differences between hemodynamic variables, including heart rate (HR), mean arterial pressure (MAP), and central venous pressure (CVP), among the survivors in each treatment group. Peak inspiratory pressure rose in all three groups but at a much higher rate in group C (P < 0.05). In contrast with the moderate effects of UTI on the above parameters, microscopic evaluation revealed a substantial difference among treatment groups: upon the initiation of anaphylaxis, the arteriole started to reduce in diameter, but UTI prevented vasoconstriction in the arteriole in a dose-dependent manner. Similar results were observed with blood flow velocity. Because flow rate was calculated as the product of blood flow velocity and vascular cross-sectional area proportional to the square of the vessel diameter, these results indicate that UTI preserves microvascular flow rate during anaphylaxis. Rabbit ear microcirculation is highly preserved in the UTI-treated groups during systemic anaphylactic shock.

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“…reported that monkeys with severe anaphyalactic shock tended to have higher systemic resistance than monkeys with mild anaphylactic shock. Also, Srnedegard et al 7 observed that total peripheral resistance increased 1.5 times in anaphylactic shock in the monkey. In humans, there are some reports that systemic vascular resistance decreases'< P or increasesv'-!".…”

Section: Discussionmentioning

confidence: 94%