Real-time Monitoring of Cardiovascular Function in Rhesus Macaques Infected With Zaire ebolavirus

Abstract

Nine rhesus macaques were implanted with multisensor telemetry devices and internal jugular vein catheters before being infected with Zaire ebolavirus. All animals developed viremia, fever, a hemorrhagic rash, and typical changes of Ebola hemorrhagic fever in clinical laboratory tests. Three macaques unexpectedly survived this usually lethal disease, making it possible to compare physiological parameters in lethally challenged animals and survivors. After the onset of fever, lethal illness was characterized by a decline in mean arterial blood pressure, an increase in pulse and respiratory rate, lactic acidosis, and renal failure. Survivors showed less pronounced change in these parameters. Four macaques were randomized to receive supplemental volumes of intravenous normal saline when they became hypotensive. Although those animals had less severe renal compromise, no apparent survival benefit was observed. This is the first report of continuous physiologic monitoring in filovirus-infected nonhuman primates and the first to attempt cardiovascular support with intravenous fluids.

Delivering Prolonged Intensive Care to a Non-human Primate: A High Fidelity Animal Model of Critical Illness

“…This increased arousal frequently required sedation boluses. This diurnal pattern has been reported previously 20 . For the fourth animal, we implemented scheduled bolus doses of midazolam (0.1 mg/kg dose) 30–45 minutes prior to the anticipated arousal period.…”

“…An alternate approach is implantable telemetry. There exists a range of devices with variable capabilities 20, 27 . They appear to provide accurate and continuous data, but are costly and require pre-experiment implantation followed by a substantial recovery period.…”

“…A final challenge centres on timely administration of medications. Implanted catheters in trained animals have been used successfully, but are limited by the number of lumens and by animal compliance 20 . Treatment approaches that would involve more than one drug become much less feasible.…”

Animal models for ebolavirus countermeasures discovery: what defines a useful model?

“…Great elevations in liver enzymes AST and ALT are seen in baboon serum samples, as well as marked hepatocellular necrosis upon post-mortem analysis [62,76,77]. Renal function is compromised in baboons, with serum creatinine (CRE) and blood urea nitrogen (BUN) levels rising two to three times higher than normal levels have been reported for baboons, humans and research macaque species [76,85]. Detailed reports of histopathological analysis of post-mortem tissues and serum and tissue viral loads are not thoroughly reported for baboons [78].…”

Surgical Infection Society Statement on Ebola Hemorrhagic Fever

“…In one animal study, Ebola caused hypotension, tachycardia, tachypnea, acidosis, and acute kidney injury. Treatment with normal saline attenuated the renal injury, but did not affect mortality [11]. At present, no specific recommendations can be made regarding how to manage patients with Ebola who are critically ill.…”