Pharmaceutical use by U.S. astronauts on space shuttle missions.

We evaluated in-flight use of medications from astronaut debriefings after 79 U.S. Space Shuttle missions. From the 219 records obtained (each representing one person-flight), 94% included some medication being taken during flight; of that number, 47% were for space motion sickness, 45% for sleep disturbances, and smaller percentages for headache, backache, and sinus congestion. Drugs were taken most often orally, followed in decreasing order of frequency by intranasal, intramuscular, and rectal routes. Drugs for space motion sickness were taken mostly during the first 2 d of flight, drugs for pain during the first 4 d, and drugs for sleeplessness and sinus congestion were taken consistently for 9 flight days. About 85% of all doses had no reported side effects, and most of the side effects that were reported happened during the first mission day. About 80% of the drug-dose events were perceived effective by the recipients; most of the reports of ineffectiveness occurred during the first mission day. Promethazine, the only drug given by three different routes (orally, intramuscularly, and rectally), was most effective and had minimal side effects when taken intramuscularly. This information, although useful, should be expanded to include objective measures of effectiveness so that therapeutic efficacy can be assessed during flight.

Saccule contribution to immediate early gene induction in the gerbil brainstem with posterior canal galvanic or hypergravity stimulation.

Immunolabeling patterns of the immediate early gene-related protein Fos in the gerbil brainstem were studied following stimulation of the sacculus by both hypergravity and galvanic stimulation. Head-restrained, alert animals were exposed to a prolonged (1 h) inertial vector of 2 G (19.6 m/s2) head acceleration directed in a dorso-ventral head axis to maximally stimulate the sacculus. Fos-defined immunoreactivity was quantified, and the results compared to a control group. The hypergravity stimulus produced Fos immunolabeling in the dorsomedial cell column (dmcc) of the inferior olive independently of other subnuclei. Similar dmcc labeling was induced by a 30 min galvanic stimulus of up to -100 microA applied through a stimulating electrode placed unilaterally on the bony labyrinth overlying the posterior canal (PC). The pattern of vestibular afferent firing activity induced by this galvanic stimulus was quantified in anesthetized gerbils by simultaneously recording from Scarpa's ganglion. Only saccular and PC afferent neurons exhibited increases in average firing rates of 200-300%, suggesting a pattern of current spread involving only PC and saccular afferent neurons at this level of stimulation. These results suggest that alteration in saccular afferent firing rates are sufficient to induce Fos-defined genomic activation of the dmcc, and lend further evidence to the existence of a functional vestibulo-olivary-cerebellar pathway of adaptation to novel gravito-inertial environments.

Long-term microvascular response to hydralazine in spontaneously hypertensive rats.

Chronic microcirculatory alterations produced by prolonged use of a vasoactive drug were repeatedly observed in the same skeletal muscle vessels of the dorsal microcirculatory chamber. Arterioles and venules with diameters averaging from 70 to 90 microns, the size range contributing most to peripheral vascular resistance, were measured daily for 6 days to determine differences in diameter, tortuosity, and number of branches. Hydralazine was given as a subcutaneous pellet (2.5 mg), with a release life of 21 days. Hydralazine caused a 39% dilation in arterioles of Wistar-Kyoto rats (WKY) at 3 hours but only an 8% dilation in those of spontaneously hypertensive rats (SHR). At 6 hours, arterioles in both groups were similarly dilated (30-33%). Beyond 6 hours, both SHR and WKY arterioles returned to their prehydralazine control diameter, even though arterial pressure was still reduced. By Day 6, in WKY, but not SHR, there was an increase in the tortuosity of arterioles and a tendency for an increase in their number. Venous diameter was also increased on Day 6, consistent with the fluid retention effect of hydralazine. These data indicate that some so-called vasodilators may cause long-term alterations in growth of vessels rather than an increase in vessel caliber.

Correlation of macro and micro cardiovascular function during weightlessness and simulated weightlessness.

The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermo-neutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the performed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.