HEAT TRANSFER IN PERFUSED TISSUE: 1948 TO 1998

In Volume 1 of the Journal of Applied Physiology, H. H. Pennes published a report (reproduced here) of heat transfer in the human forearm. The report included multiple measurements of temperature within the forearms of several brave subjects and a theoretical analysis of the experimental results. The analytic model has been extensively applied but also criticized over the ensuing 50 years, and its strengths and errors are assessed by E. H. Wissler in a paper published in this 50-year anniversary issue of the Journal (p. 35). The contributions of both Pennes and Wissler are discussed in an Invited Editorial by Nelson (p. 2).

	DOES VEGF CONTRIBUTE TO HIGH-ALTITUDE CEREBRAL EDEMA?

Ascent to high altitude has long been known to produce both cerebral and pulmonary edema (HACE and HAPE, respectively). On the basis of lung lavage fluid analysis, the latter in particular has been shown to have an inflammatory component. Thus HAPE and HACE may well involve more than altered vascular pressure alone. Vascular endothelial growth factor (VEGF), essential to normal angiogenesis, is known to be hypoxia inducible in many tissues and also causes increased microvascular permeability. Xu and Severinghaus (p. 53) report that acute hypoxia increases VEGF mRNA and protein levels in rat brain and also increases VEGF-receptor mRNA. These results do not prove that VEGF is responsible for HACE (or HAPE), but they are consistent with that hypothesis. It will be of great interest to learn whether VEGF inhibition with the use of antibodies, soluble VEGF receptor, or antisense strategies can prevent or attenuate HACE.

	ASYMMETRY IN SNEEZING

Mechanical or electrical stimulation of nasal afferents evokes activation of nasal muscles and, frequently, sneezing. Sekizawa et al. (p. 123) investigated the response to unilateral nasal probing or stimulation of the ethmoidal nerve. Stimulation on either side evoked greater activation of nasal muscles on the contralateral side and a greater increase in resistance to expiratory flow through the contralateral nostril. This asymmetrical response is presumably of value for clearing irritants and secretions from the ipsilateral nostril. The underlying neurophysiology remains obscure.

	VASCULAR RESPONSES TO HEAT STRESS IN HYPERTENSIVE SUBJECTS

During dynamic exercise in the heat, increases in skin blood flow are attenuated in hypertensive subjects, relative to controls. Does this attenuation reflect enhanced vasoconstrictor activity, reduced vasodilator activity, or both? Kellogg et al. (p. 175) measured mean arterial pressure and forearm blood flow in hypertensive subjects and in controls during passive heat stress in water-perfused suits. Bretylium tosylate was used to block active vasoconstriction in a small area of skin. During normothermia, forearm vascular conductance in hypertensive subjects was decreased but it increased with heat stress to values similar to those in controls. Concurrent increases in skin blood flow were unaffected by bretylium treatment. Thus hypertensive and normotensive subjects respond similarly to passive heat stress.

	ENERGY COST OF PHYSICAL ACTIVITY IN PRETERM INFANTS

How much of an infant's metabolic work is devoted to movement? Thureen et al. (p. 223) measured physical activity with a special force plate and total energy expenditure by indirect calorimetry in healthy preterm infants 3-4 wk after birth. Physical activity accounted for ~3% of total daily energy expenditure, somewhat less than estimates for full-term infants. The energy cost of physical activity showed a wide dynamic range, varying 30-fold between quiet sleep and active crying.

	MENISCUS FORMATION OF INSTILLED SURFACTANT

On theoretical grounds, the formation of menisci in lung airways during surfactant-replacement therapy might contribute to a more homogeneous distribution of surfactant in the lung periphery. Espinosa and Kamm (p. 266) studied the effects of several physical variables on meniscus formation during a bolus injection of surfactant in an in vitro airway model. Meniscus formation occurred when the Stokes number (the ratio of viscous to gravitational effects) exceeded 0.004Re^1/3, where Re is the Reynolds number (the ratio of inertial to viscous effects). Meniscus formation was enhanced by rapid injection, a high bolus viscosity, and a small tracheal inclination with respect to gravity.

	EXERCISE HYPERVENTILATION AND THERMAL DRIVE

During mild-to-moderate steady-state exercise in humans, alveolar ventilation rises in proportion to CO₂ production, and arterial PCO₂ is regulated within a few millimeters of Hg of resting levels. On the other hand, hyperventilation with respiratory alkalosis is a common response to even mild exercise in quadrupeds, and the degree of hyperventilation increases with exercise intensity. Entin and colleagues (p. 318) studied exercising sheep to determine the role of a rising body temperature in explaining the hyperventilatory response to exercise. They found that the rise in rectal temperature correlated closely with hyperventilation. In fact, almost 80% of the variance in arterial PCO₂ with increasing exercise was accounted for by an increasing rectal temperature. Whether the rising temperature has a direct, i.e., hypothalamic, effect on ventilatory control or exerts its influence indirectly, by affecting other mechanisms of exercise hyperpnea, remains unknown.

	HOW IS EXTRACELLULAR K+ CLEARED FROM EXERCISING MUSCLE?

Working skeletal muscle releases K⁺ as a result of the excitation-contraction process. This K⁺ must either be taken up by surrounding cells or cleared by the circulation to preserve contractile function. Increases in interstitial and plasma K⁺ concentration, as a result of heavy muscular exercise, have been reported to reach millimolar quantities. In an attempt to evaluate the role of erythrocytes in clearing K⁺ from working human muscle, Maassen et al. (p. 326) conducted two sets of experiments. First, they measured erythrocyte size and K⁺ content in the venous effluent of working forearms. Second, they measured, in vitro, ⁸⁶Rb⁺ uptake by fresh human erythrocytes under conditions simulating those in plasma of working muscle. The data do not support a significant role of erythrocytes in clearing K⁺ from working human skeletal muscle.

	A ROLE FOR NITRIC OXIDE IN THE HYPOXIC VENTILATORY RESPONSE?

The hypoxic ventilatory response (HVR) in humans is biphasic, consisting of an initial hyperpneic response followed by a gradual decline in ventilation. Direct central effects of hypoxia may account for the decline and may also modulate the initial response. The peak HVR has been shown to be augmented by a preceding hyperoxic exposure. Gozal et al. (p. 372) postulate that brain nitric oxide plays a role in the biphasic HVR and its potentiation by a preceding hyperoxic exposure. They have examined the possible role of nitric oxide synthase (NOS) in this hyperoxia-induced potentiation of HVR in conscious adult rats. Pretreatment with a selective NOS inhibitor blocked HVR potentiation in O₂-exposed animals, indicating that NOS activation may be involved in the mechanism of HVR potentiation by prior hyperoxia.