Radiotelemetry is the "state of the art" for monitoring physiological functions in awake and freely moving laboratory animals, while minimizing stress artifacts. For researchers, especially those in the fields of pharmacology and toxicology, the technique provides a valuable tool for defining the physiological and pathophysiological consequences derived from advances molecular, cellular, and tissue biology and in predicting the effectiveness and safety of new compounds in humans. There is ample evidence that radiotelemetry systems for measuring physiological functions has been sufficiently validated. Today, the technology is an important tool for collection of a growing number of physiological parameters, for contributing to animal welfare (reduction and refinement alternatives), and for reducing overall animal research costs.
A simple and reliable means for accurate, chronic measurement of pulsatile blood pressure (BP) from conscious, freely moving laboratory mice was developed and validated. The newly developed device consists of a small (1.9 ml, 3.4 g), fully implantable radiotelemetry transmitter. Initial frequency response tests showed an adequate dynamic response; the average -3-dB point found in five transmitters was 145 +/- 14 (SD) Hz. BP, heart rate, and locomotor activity were recorded from 16 chronically (30-150 days) implanted mice. Mean arterial and pulse pressure, checked at regular intervals, ranged from 90-140 mmHg and from 30-50 mmHg, respectively, throughout the study. Transmitter BP measurements were validated against a Millar 1.4-Fr. transducer-tipped catheter. The mean error of the transmitters for diastolic pressures was +1.1 +/- 6.9 mmHg (n = 7). The error for systolic pressures was, on average, 2.7 +/- 3.9 mmHg larger. This new device accurately monitors BP, heart rate, and locomotor activity in conscious, untethered, freely moving mice living in their home cages for periods of at least 150 days.
The clinical use of the antitumour agent, doxorubicin, is largely limited by the development of a cumulative dose‐related cardiotoxicity. This toxicity is generally believed to be caused by the formation of oxygen free radicals. In earlier studies it was established that flavonoids, naturally occurring antioxidants, can provide some degree of protection. In this study we investigated whether 7‐monohydroxyethylrutoside (monoHER), a powerful antioxidative flavonoid with extremely low toxicity, can provide protection to an extent comparable to the clinically successful Cardioxane (ICRF‐187).
Balb/c mice of 20–25 g were equipped i.p. with a telemeter to measure ECG. They were given 6 i.v. doses of doxorubicin (4 mg kg −1) at weekly intervals. ICRF‐187 (50 mg kg−1) or monoHER (500 mg kg−1) were administered i.p. 1 h before doxorubicin administration. In the 2 monoHER groups the treatment continued with either 1 or 4 additional injections per week. A saline and monoHER treated group served as controls. After these 6 weeks, they were observed for another 2 weeks.
At the end of this study (week 8) the ST interval had increased by 16.7 ±2.7 ms (mean ± s.e.mean) in doxorubicin‐treated mice. At that time, the ST interval had increased by only 1.8 ±0.9 ms in ICRF‐187 co‐mediated mice and in monoHER co‐medicated mice by only 1.7 ±0.8 and 5.1 ± 1.7 ms (5‐ and 2‐day schedule, respectively, all P< 0.001 relative to doxorubicin and not significantly different from control). The ECG of the control animals did not change during the entire study. The QRS complex did not change in either group.
It can be concluded that monoHER protects against doxorubicin‐induced cardiotoxicity and merits further evaluation in this respect.
Implantable radio-telemetry methodology, allowing for continuous recording of pulmonary haemodynamics, has previously been used to assess effects of therapy on development and treatment of pulmonary hypertension. In the original procedure, rats were subjected to invasive thoracic surgery, which imposes significant stress that may disturb critical aspects of the cardiovascular system and delay recovery. In the present study, we describe and compare the original trans-thoracic approach with a new, simpler trans-diaphragm approach for catheter placement, which avoids the need for surgical invasion of the thorax. Satisfactory overall success rates up to 75% were achieved in both approaches, and right ventricular pressures and heart and respiratory rates normalised within 2 weeks. However, recovery was significantly faster in trans-diaphragm than in transthoracic operated animals (6.4±0.5 vs 9.5±1.1 days, respectively; p<0.05). Stable right ventricular pressures were recorded for more than 4 months, and pressure changes, induced by monocrotaline or pulmonary embolisms, were readily detected. The data demonstrate that right ventricular telemetry is a practicable procedure and a useful tool in pulmonary hypertension research in rats, especially when used in combination with echocardiography. We conclude that the described trans-diaphragm approach should be considered as the method of choice, for it is less invasive and simpler to perform.
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