Introduction of a new medical procedure: a novel approach.

Before it is permitted for general use, a newly developed drug or medical device must undergo a series of pre-clinical testing and clinical trials to prove safety and efficacy. However, new medical procedures--even highly sophisticated and ethically controversial ones, such as organ transplants and I.V.F. do not require any clearance from regulatory authorities. This is an undesirable situation, which can be corrected by limiting legal liability for those who opt to perform new medical procedures as part of clinical trials. By this means we shall encourage a more prudent and better regulated introduction of new technologies into medical practice.

Statistical criteria for using short-term measurements as an index of 24-hour mean arterial pressure in unanesthetized unrestrained dogs.

This study assessed the statistical validity of short time-interval measurements as estimators of true 24 hour mean arterial pressure in unanesthetized, unrestrained dogs. 24 hour intra-arterial pressure recordings were obtained using a stable FM telemetry system. The 24 hour pressure measurements approximated a normal distribution whose variance was inversely related to the selected averaging interval. Given the variance of a normal distribution one can calculate the 95% confidence interval for any single random measurement. Conversely the number of random samples necessary to be within a prescribed confidence interval can be determined. In this study, the 95% confidence interval for a single, random 30 minute arterial pressure average was calculated to be 11.2 mmHg. Only 4.8 +/- 1.4% of 480 individual 30 minute arterial pressure measurements fell beyond this confidence interval. These outlying values were distributed throughout the 24 hour period. The data suggest that randomly chosen short time-interval measurements may be a valid index of true 24 hour mean pressure if the average variance of a population is known and confidence intervals are defined.

Moiré deflectometry with pure sinusoidal gratings.

The effect of using a sinusoidal grating instead of a Ronchi ruling as the object grating in moiré deflectometry is discussed and demonstrated. The method reduces the diffraction blur, which hinders the use of the conventional moiré deflectometer for objects of locally varying focal lengths. The technique combines most of the advantages of moiré deflectometry and shearing interferometry.

Inhibition of renin release following left circumflex bradykinin injection in dogs.

We examined the renin secretory response to bradykinin (BK) injection into the left circumflex coronary artery (LCx) in dogs. Studies were conducted in anesthetized, carotid sinus denervated dogs which had been maintained on a low sodium diet. A 25 ga needle was inserted into the LCx for injection of BK (0.15 micrograms/kg). The rate of renin secretion (RS) was obtained during a 30 min control period, at 5 min after a non-hypotensive hemorrhage (10 ml/kg), at 1, 3 and 5 min after BK injection and at 15 min after the reinfusion of withdrawn blood. Four series of studies were conducted. Series I: BK injection into the LCx, Series II: saline injection into the LCx (sham), Series III: intravenous injection of BK, and Series IV: BK injection into the LCx in dogs with prior renal denervation. RS was suppressed by 80% (P less than 0.05) 5 min after injection of BK into the LCx. Saline injection (sham) into the LCx or intravenous BK administration did not inhibit RS. Furthermore, suppression of RS was not present in dogs with prior renal denervation. These results indicate that BK injection into the LCx causes a prompt reduction in the rate of RS and that this response is reflexively mediated by the renal nerves.

Ultradian oscillations in blood pressure and heart rate in free-running dogs.

A long-term (14-24 h) telemetry recording of mean arterial pressure (MAP) and heart rate (HR) was obtained from conscious unrestrained dogs (n = 9) maintained in a closed environment. MAP and HR records were analyzed for their harmonic content by the fast Fourier transform method. The power spectral density functions of MAP and HR clearly revealed the existence of coherent ultradian rhythms of MAP and HR with a period of 1-2 h. HR and MAP are in phase and sustained during a 24-h period. To elucidate the nature of these rhythms, two additional studies were conducted (n = 4) in which clonidine (200 micrograms/kg) was administered systemically. In series I, a 7-h control period preceded the administration of clonidine, whereas in series II the order was reversed. Control (series I) and recovery (series II) periods were compared with a 0- to 7-h postinjection period. The results show that clonidine drastically and significantly reduces the amplitude of both MAP and HR oscillations for an average period of 7 h. This response was very consistent in both series and in all four dogs. These results implicate the central nervous system as the origin of these rhythms.

Crystal-controlled telemetry system for long-term acquisition of physiological data.

A crystal-controlled telemetry system was developed for long-term high-reliability recording of blood pressure in unrestrained animals. The miniaturized transducer-transmitter system is powered by two lithium batteries that allow for more than 200 h of continuous recording of blood pressure before battery replacement. The total system has a flat frequency response of 0-25 Hz and a time stability of +/- 1 mmHg/day. Linearity is better than 0.5%. The high degree of dependability of the system permits us to perform continuous, unattended, around-the-clock recordings of pressure and heart rate in unrestrained animals. Very high dependability is achieved by the use of a novel piezoresistive blood pressure transducer and by the inherent stability of the crystal-controlled radio-frequency oscillator of the transmitter. The receiver is also crystal tuned to the measured transmitter frequency. This transmitter-receiver frequency locking ensures very reliable reception of the telemetered signal.

Central and peripheral adrenergic modulation of carotid sinus-induced renin release.

To study central and peripheral mechanisms that regulate the level of circulating renin during activation of the carotid sinus baroreflex, both carotid sinuses were isolated and perfused at constant flow in chloralase-anesthetized dogs. Sinus pressure was controlled by an adjustable reservoir while systemic pressure was stabilized using an external chamber. Arterial renin activity, measured by radioimmunoassay, was increased during sinus hypotension only if systemic pressure was held constant. The renin response was eliminated by either sinus or renal denervation. Administration of propranolol (iv) or phentolamine directly into the renal artery totally blocked the increase in renin during activation of the reflex. Perfusion of a beta-adrenergic blocker (propranolol) or an alpha-adrenergic blocker (phentolamine) through the third and fourth cerebroventricles had no effect on the increase in renin during sinus hypotension, whereas centrally administered clonidine, and alpha-agonist, blocked the response. We conclude that the sinus reflex arc affecting renin release involves not only activation of peripheral alpha- and beta-adrenergic receptors in the kidney but also inhibition of central alpha-adrenergic receptors. No evidence for central beta-involvement was found.

Acute inhibition of renin release during left circumflex coronary occlusion in dogs.

We examined the reflex effect of brief left circumflex coronary artery occlusion (CAO) on renal blood flow (RBF) and renin secretion (RS). Studies were conducted in alpha-chloralose-anesthetized dogs maintained on a salt-free diet for at least 3 days. A snare was placed around the left circumflex artery near its origin. The left renal artery and vein were exposed via flank incision, a flow probe was placed around the artery, and a curved needle was inserted into the vein for collection of renal venous blood. Values of blood pressure (BP), RBF, and RS were obtained for a 30-min control period, 4 min after the completion of a 10-ml/kg hemorrhage, 1 and 5 min after CAO, and 15 min after reinfusion. The CAO consisted of two 1-min occlusions separated by a 1-min interval. The results indicate that CAO reflexively inhibits the RS response to nonhypotensive hemorrhage and prevents renal vasoconstriction (P less than 0.05, n = 7). Both effects were completely abolished after vagotomy (n = 5). Renal denervation also abolished the response (n = 5). No response was observed during identical time controls (n = 5). The response was more pronounced in dogs with carotid sinus denervation, even though CAO resulted in marked reductions in BP (20%) under these conditions. These results demonstrate the presence of a cardiorenal reflex that can be activated by myocardial hypoxia and that acutely suppresses RS. This response is more pronounced in the absence of carotid sinus buffering.