Human cerebral malaria (HCM), a complication of plasmodium falciparum infections, is the cause of over 1 million deaths worldwide each year, more deaths than any other parasitic disease. It is important to understand how to best treat HCM. There are many reports of conduction system disturbances in humans with malaria. Little is known, however, about the electrocardiographic (ECG) features of mice with experimental malaria.
Instrumentation such as the ECGenie makes the investigation of ECG and autonomic disturbances in mouse models of parasitic infections such as malaria and trypanosoma cruzi [Chagas disease]possible. Furthermore, many anti-malarial drugs unfortunately have negative consequences on the heart. Study of electrocardiographic and autonomic disturbances in mouse models of parasitic disease may accelerate the advancement of therapies.
In a recent study published in the Malaria Journal, optimal treatment was examined by looking at nimodipine dosage in conjunction with artesunate in a mouse model of malaria. Because high doses of dihydropyridine calcium channel blocker nimodipine could potentially result in hypotension, bradycardia, arrhythmias, and even death, an alternative form of treatment was studied in which low doses and alternative delivery systems of nimodipine were administrated to mice with late-stage ECM (the experimental model of cerebral malaria). To measure the effectiveness of the treatment, several key measurements were taken; including ECG recordings (with the help of Mouse Specifics Inc. EzCG analysis software) and arterial pressure measurements.
The ECGenie is the fastest, easiest, and friendliest way to determine whether your gene defect or drug results in cardiac disturbances – without surgery or anesthetic. That’s right – telemetric implants are not needed! Simply place the newly born, aged, recovering, or dosed animal on the patented ECGenie platform and monitor its full electrocardiogram. The ECGenie : Non-invasive, fast, and easy ECG in awake lab animals.
“…better data from every mouse!”
[Click here to see EzCG software in action with the ECGenie!] ECGs were analyzed for heart rate, and heart rate variability, in the time and frequency domain. Arterial pressure was measured for systolic, diastolic, and mean arterial blood pressure data.
Remarkably there was a nearly 50% reduction in heart rate in mice with malaria. The study also reported profound hypothermia in infected mice. The ~5 ºC reduction in core body temperature could account for about a ~125 beat-per-minute reduction in heart rate. Heart rate variability was significantly increased in infected mice. Low and continuous delivery of nimodipine improved ECM mouse survival alongside treatment with artesunate. The lower dose treatment, 0.5mg/kg/day, as compared with the higher dose of 2.5 mg/kg/day, had higher absolute risk reduction rates and a lower number needed to treat. The lower dose showed an improved survival.
It has been previously shown that nimodipine could potentially cause detrimental effects in humans, such as hypotension, bradycardia and arrhythmias. Therefore, it is very important to find a method of treatments which avoids such side effects. This study showed that slow and low doses of nimodipine have no significant effect on such cardiovascular parameters. In fact, the treatment even improved cardiac alterations in mice with late-stage ECM, showing the potential for adjunctive therapy. The cause of the profound hypothermia and bradycardia is not clear from this study. However, the observations point to important nuances in this animal model of malaria. Moreover, the findings underscore the utility of non-invasive electrocardiographic monitoring in mice with parasitic disease to advance the development of effective drugs with minimal cardiotoxicity.