HYPOXIC HYPOMETABOLISM IN INFANT MAMMALS

In many species of newborn mammals, exposure to hypoxia leads to a reduction in metabolic rate. Rohlicek et al. (p. 763) questioned whether this is a regulated response or whether it reflects limitation of O₂ availability. Arterial O₂ content or saturation, venous PO₂ or saturation, and O₂ consumption were measured during normoxia and hypoxia in young puppies at ambient temperatures of 30 and 20°C. Hypometabolism occurred at both temperatures but required a lower inspired O₂ in the warm environment (10% vs. 12% O₂). With hypometabolism, the graphs of O₂ consumption vs. measures of O₂ availability had lower slopes in the warm vs. the cold environment. Thus, during a cold stimulus, a higher metabolism was sustained at any given level of oxygenation. These results indicate that hypometabolism during hypoxia is not due to limitation of O₂ availability but is probably a regulated phenomenon. The paper is discussed in an Invited Editorial by Gautier (p. 761).

	OSMOTIC CONDUCTANCE OF PULMONARY CAPILLARIES

The osmotic conductance of the pulmonary capillaries is a useful indicator of the integrity of the capillary endothelium. Karch and Lee (p. 769) have taken advantage of the ability to measure online very small density changes in blood to develop a method for measuring the pulmonary capillary osmotic conductivity in vivo. The blood density measurements are accomplished by measuring the resonance frequency of a small glass U tube containing blood. The density changes in aortic blood observed during a 20-s intravenous infusion of a hyperosmotic solution reflect the osmotically driven water movement between lung tissue and blood. The data obtained allowed for estimation of the pulmonary capillary reflection coefficient-filtration coefficient product for test solutes such as sodium chloride, urea, and various sugar molecules.

	A ROLE FOR CENTRAL NERVOUS SYSTEM GLUTAMATE IN THE HYPOXIC VENTILATORY RESPONSE?

McCormick et al. (p. 830) examined extracellular glutamate levels by microdialysis in the region of the nucleus tractus solitarii (NTS) while recording phrenic nerve activity in anesthetized mechanically ventilated piglets during hypoxia coupled with hypothermia or normothermia. During normothermia, isocapnic hypoxia induced an average sustained increase in minute phrenic activity and glutamate levels, along with a decrease in O₂ consumption. However, during hypothermia, minute phrenic activity decreased during hypoxia. Glutamate levels and O₂ consumption also decreased. A linear relationship was found between minute phrenic activity and glutamate levels when data from both normothermic and hypothermic exposures were combined. Thus decreases in minute phrenic activity during hypoxia appear to be linked to, and possibly mediated by, decreased glutamate concentrations in the NTS.

	LIMITS OF EXERCISE IN HOT ENVIRONMENTS

Is there a critical level of body temperature, beyond which animals will not continue voluntary exercise in the heat? Fuller et al. (p. 877) measured abdominal and brain temperatures in rats during voluntary exercise in a variety of hot environments. Running time to fatigue varied with the severity of the heat stress, but abdominal and brain temperatures at the time of fatigue were the same in all conditions. Brain temperature consistently exceeded abdominal temperature throughout exercise, so selective brain cooling did not occur under the conditions of the study. These results support a temperature limit for voluntary exercise in the heat.

	EXERCISE TRAINING AND CORONARY VESSEL CONSTRICTOR RESPONSES

Coronary resistance arteries from exercise-trained pigs exhibit enhanced myogenic reactivity. Laughlin and Muller (p. 884) tested the hypothesis that exercise training enhances the responses of these vessels to constrictor stimuli, namely, acetylcholine, endothelin-1, KCl, and the Ca²⁺ agonist Bay K 8644. The first two agents constrict coronary arteries by receptor-mediated mechanisms, whereas the latter two do so by opening voltage-gated Ca²⁺ channels. The responses caused by both mechanisms were similar in arteries isolated from trained and sedentary pigs. The authors concluded that training enhances the vasoconstrictor responses of coronary arteries by myogenic mechanisms and that this effect does not involve L-type Ca²⁺ channels or receptor-mediated second-messenger systems used by acetylcholine or endothelin-1.

	DOES THE BRONCHIAL CIRCULATION EXACERBATE SMOKE INHALATION INJURY?

The bronchial circulation may provide protection against lung injury, for example, after ischemia of the pulmonary circulation. However, in the case of smoke inhalation, the existence of the bronchial circulation may exacerbate the pulmonary edema that results. Sakurai et al. (p. 980) examined the effect of decreases in bronchial blood flow on the increases in lung lymph flow, lung wet-to-dry weight ratio, and plasma protein reflection coefficient of the lung caused by smoke inhalation in sheep. The authors compared sheep with and without bronchial arterial ablation produced by injecting ethanol into the bronchial artery, followed by bronchial artery ligation. The reflection coefficient was higher and the wet-to-dry weight ratio was lower with ablated bronchial circulation 24 h after an acute exposure to cotton smoke. Therefore, at least during the studied phase of the response to smoke inhalation, the bronchial circulation appears to have a detrimental effect.

	WHAT LIMITS O2 UPTAKE IN EXERCISE?

Is O₂ consumption during exercise limited by constraints on O₂ supply or by the capacity of the metabolic machinery of the exercising muscles? Richardson et al. (p. 995) addressed this long-standing question by using an allosteric modifier of hemoglobin to shift the O₂ dissociation curve to the right in anesthetized dogs. This shift enhanced the PO₂ gradient driving the diffusive step of O₂ transport to an in situ hindlimb muscle preparation during electrical stimulation of the motor nerve. Convective O₂ transport was maintained by ventilation with 100% O₂ and pump perfusion of the muscle. At constant convective O₂ delivery, an increase in the PO₂ at 50% saturation of hemoglobin (P₅₀) led to increased O₂ extraction and increased maximal O₂ consumption. These changes are presented as evidence that the diffusive transport of O₂ to muscle is an important determinant of maximal O₂ uptake when P₅₀ is normal.

	ANDEAN HIGH-ALTITUDE NATIVES RESIDING AT SEA LEVEL HAVE NORMAL VENTILATORY RESPONSES TO HYPOXIA

Andean high-altitude natives are well known for their blunted ventilatory responses to acute hypoxia. Vargas and associates (p. 1024) asked whether this reduced responsiveness is reversible after the highlanders move to sea level. They used brief isocapnic hypoxic response tests to study subjects who had been born and raised above the altitude of 3,500 m but had moved to sea level several years ago. Findings show the hypoxic responses in these former natives of high altitude to be comparable to those of sea-level natives. Although these data are in conflict with other published studies, this appears to be the most comprehensive examination of this problem to date: it clearly implies that hypoxic ventilatory "insensitivity" is completely reversible.

	VIRAL RESPIRATORY INFECTION AND HYPOXIA-INDUCED PULMONARY EDEMA

The mechanisms responsible for high-altitude pulmonary edema (HAPE) are unknown and difficult to study, largely because it is not clear that any species other than humans are susceptible. Thus there has been considerable interest in possible animal models of HAPE. Carpenter et al. (p. 1048) were struck by the clinical correlation between preexisting respiratory infection and the incidence of HAPE in children. Thus they addressed the hypothesis that previous viral infection might produce an acquired susceptibility to HAPE. To evaluate this hypothesis, they inoculated weanling rats with a murine parainfluenza virus that produced a mild respiratory infection. Six days later, after the animals had apparently recovered from the infection, they were placed in 10% O₂ for 24 h. Compared with control groups, the previously infected animals had greater perivascular cuffing, lung-to-body weight ratios, and lung protein leak in response to the hypoxic exposure. The authors conclude that the infection had, in fact, made the rats more susceptible to the increases in pulmonary vascular permeability brought about by hypoxia.