Thermoregulatory-induced compromise of muscle blood flow in ponies during intense exercise in the heat: a contributor to the onset of fatigue?

Cardiac output (Q) and tissue blood flows (BF) were measured in four ponies at rest, after 30 min of moderate exercise (ME) (approximately 30% VO2max) and following moderately intense exercise (M-IE) (approximately 65%) until fatigue, in a mildly hot (MH) environment (dry bulb temperature = 41 degrees C, wet bulb temperature = 27.5 degrees C). Exercise at both intensities resulted in increases in Q (15.6 +/- 1.7 [rest] vs. 35.8 +/- 2.6 [ME] vs. 48.6 +/- 3.9 [M-IE] l/min) and VO2 (4.7 +/- 0.9 vs. 24.5 +/- 1.2 vs. 55.8 +/- 5.8 ml/kg/min). When compared to ME, M-IE resulted in decreases in BF to the skin (approximately 15%), nonworking muscle (46%), fat (93%), gut (56%), kidneys (57%), CNS (31-66%) and an increase in BF to respiratory (68%), limb (98.5%) and cardiac (50%) muscles. In contrast, BF to working muscle during ME in thermoneutral (TN) conditions (McConaghy et al. 2002) was higher than found during ME in MH. We calculated that limb BF was approximately 25% lower for ME in MH vs. ME in TN. Similarly, we estimated that limb BF during M-IE in MH was approximately 25% lower than for M-IE in TN. Attenuation of the increases in muscle BF during exercise in the heat may be a determinant of the onset of fatigue.

Fluorescent microspheres are superior to radioactive microspheres in chronic blood flow measurements.

The accuracy of the fluorescent (FM) and radioactive microsphere (RM) techniques is similar in acute experiments but has not been established in chronic experiments. In the present study various combinations (at least pairs) of FM and/or RM labels were injected simultaneously between 2 mo and 5 min before each animal was killed. Blood flow was determined in many organs. Intramethod mean difference and variation did not change over time for FM but increased significantly for RM (from 1.8 +/- 1.4 to 25.6 +/- 21.8% and from 4.4 +/- 3.2 to 32.4 +/- 23.0% at 5 min and 2 mo, respectively). Also the FM-RM intermethod mean difference and variation increased (from -0.5 +/- 8.5 to 40.8 +/- 23.8% and from 23. 6 +/- 4.6 to 71.8 +/- 34.3%, respectively). After 2 mo, blood flow estimations were 20-50% lower with the various RM, whereas brain and liver blood flow values varied even more between isotopes. Underestimation started within 1 day for 51Cr and within 2 wk for 141Ce, 95Nb, and 85Sr. We conclude that FM are superior to RM for blood flow determination in experiments lasting longer than 1 day, presumably because of leaching of isotopes from RM.

Selective brain cooling in hyperthermia: the mechanisms and medical implications.

We hypothesize that selective brain cooling (SBC) can occur in hyperthermic humans despite the fact that humans have no carotid rete, a vascular structure that facilitates countercurrent heat exchange and that is located at the base of the skull in some mammals. We postulate that an increase in emissary and angular ocular venous flows contributes to SBC. The efficiency of SBC is increased by evaporation of sweat on the head and by ventilation through the nose. A body position that increases the intravenous pressure gradient across the skull increases emissary flows and hence enhances the efficiency of SBC. The validity of using tympanic temperature as an index of brain temperature is also postulated.

A role for gastrointestinal endotoxins in enhancement of heat tolerance by physical fitness.

To further elucidate mechanisms underlying the higher heat tolerance of physically fit compared with sedentary people, we have investigated the possibility that endotoxins (of gastrointestinal origin) act, as in the normal development of fever, to raise body temperature and therefore reduce heat tolerance. In an initial series of experiments, five physically fit and four sedentary sheep were exposed twice at rest to an environment of 42/35 degrees C (dry/wet bulb temperature). When animals were given normal saline i.v., rectal temperature (Tre) rose at a significantly higher rate in sedentary than in fit animals; this confirms that heat tolerance is improved by physical fitness. Treatment with i.v. indomethacin did not affect the rate of rise of Tre in fit animals. In sedentary animals, however, Tre was lowered to approximate that of fit animals. Because indomethacin blocks prostaglandin pathways involved in endotoxin-induced fever, the indomethacin-induced improvement of heat tolerance of sedentary but not fit animals supports the contention that endotoxins play a role in determining that difference in heat tolerance. In a second series of experiments, quantitative cardiovascular measurements were made by using radioactive microspheres. Under normothermic conditions, blood flows in the brain, ileum, and diaphragm were higher in fit than in sedentary animals. During hyperthermia up to Tre of 42 degrees C (in a 42/39 degrees C environment), fit compared with sedentary animals exhibited 1) a greater increase in cardiac output, 2) an increase in blood flow through arteriovenous anastomoses to higher and better maintained levels, 3) less reduction in blood flow to the ileum, and 4) greater increase in blood flows to the myocardium, turbinates, nasal mucosa, and respiratory muscles. Endotoxins are likely to come from the gut lumen, because reduction of gut blood flow forms part of the normal response to heat stress. We suggest that improvement of heat tolerance by physical fitness is caused by a greater cardiovascular capacity that permits not only greater perfusion of heat-loss tissues but the maintenance of a better gastrointestinal tract blood supply, thereby better maintaining the normal barrier to movement of endotoxins from gut lumen to plasma. Sedentary people, with their lower cardiovascular capacity, redistribute more blood flow away from the gut during environmentally induced hyperthermia, thus allowing endotoxin-induced fever to aggravate hyperthermia.

Redistribution of cardiac output in response to heat exposure in the pony.

Radioactive microspheres were used to measure cardiac output and blood flow to most major tissues in 4 ponies at rest in thermoneutral (16 degrees C/60% RH) and mildly hot (41 degrees C/34% RH) environments. In response to heat stress there were increases in cardiac output (2-fold), respiratory frequency (5-fold), blood flow to the skin of the body (3-fold), and limbs (50%), respiratory muscles (2-fold) and the upper respiratory tract (3-fold). Ponies were able to maintain body temperature in the hot environment by increasing blood flow to the tissues involved in heat dissipation, while blood flow to all other tissues remained stable. This was achieved by increasing the cardiac output without need for reduction of blood flow to other tissues.

Selective brain cooling in the horse during exercise and environmental heat stress.

Five horses were exercised on a treadmill [to central blood temperature (Tcore) approximately 42.5 degrees C]. Three of those horses were heated at rest in a climate room (53 degrees C, 90% relative humidity) (to Tcore approximately 41.5 degrees C). Temperatures were measured in the rectum, hypothalamus (Thyp), cerebrum, and cavernous sinus (Tsinus), on the skin of the head and midside, and Tcore. When Tcore increased above 38.5 degrees C, Thyp remained 0.6 +/- 0.1 degree C (SE) lower during heat exposure and 1 +/- 0.2 degrees C lower during exercise. During heat exposure, Tsinus was 2.2 +/- 0.4 degrees C below Tcore, and during exercise, Tsinus was 5 +/- 0.9 degrees C below Tcore. Upper respiratory tract bypass during exercise in one horse resulted in substantial reductions in Tcore-Thyp to 0.4 +/- 0.3 degrees C and Tcore-Tsinus to 0.9 +/- 0.2 degrees C. Thus the horse, a species without a carotid rete, can selectively cool the brain during exercise or heat exposure; this occurs, at least in part, via cool blood within the cavernous sinus, presumably resulting principally from cooling of venous blood within the upper respiratory tract.

Selective regional vasoconstriction underlying pressor effects of galanin in anaesthetized possums compared with cats.

1. Intravenous administration of porcine galanin (5 nmol kg-1) caused a rise in mean blood pressure in the brush-tailed possum, Trichosurus vulpecula, from 58 +/- 1.6 to 106 +/- 1.6 mmHg. This effect is in contrast to the cat, in which no significant change in blood pressure was recorded in response to galanin (88 +/- 2.3 vs. 86 +/- 2.4 mmHg). 2. Cardiac output and regional blood flow distribution were assessed by distribution of radioactive microspheres in four anaesthetized possums and four cats, before and after administration of galanin. 3. Cardiac output was 289.8 +/- 14.0 ml min-1 in the cat and 189.9 +/- 25.5 ml min-1 in the possum. Galanin administration did not significantly change cardiac output in either species. 4. In the possum, galanin administration caused large increases in resistance to flow in the spleen, gut, adrenal glands, kidney, skin and carcass. The largest increase was in the kidneys, where renal blood flow fell to 6% of control levels. 5. In the cat, changes in resistance were small. Small increases in resistance to flow in muscle and carcass were offset by small decreases in resistance in the lungs and kidneys. 6. The results suggest that the pressor effect of galanin in the possum is the result of direct vasoconstrictor action in several vascular beds, in contrast to the cat, in which such effects are few and weak.

Wool production and blood supply to skin and other tissues in sheep.

Quantitative measurements of blood flow (BF) to skin and several other tissues were made using radioactive microspheres in conscious sheep. The sheep were from established flocks that had been selectively bred for greater (Fleece plus) or lesser (Fleece minus) wool production. The BF rate per unit area of wool-bearing skin was significantly greater in the Fleece plus (n = 9) than in the Fleece minus (n = 6) group, but the correlation between skin BF and the wool growth rate in individual animals was modest (r = .581). There was a strong, positive correlation (r = .813) between wool production and pineal BF. Other tissues that exhibited significant BF differences between the two groups included adrenal glands and fat, which were greater in Fleece plus sheep, and thyroid glands, reticulum, rumen, and extremity skin (non-wool-bearing), which were lesser in Fleece plus sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for skin microvascular compartmentalization by laser-Doppler and photoplethysmographic techniques.

Indices of perfusion were obtained using commercial laser-Doppler instruments with differing wavelengths on metatarsal skin of sheep (which is abundant with AVAs) and compared with quantitative measurements of AVA and capillary blood flow using microspheres; an infra-red photoplethysmograph was also compared. The data provide physiological evidence that laser-Doppler instruments of longer wavelength sense to a greater depth, and our photoplethysmograph behaves similarly to a "near-infra-red" laser. Thus, we suggest that near-infra-red light, either laser-Doppler or photoplethysmograph, should be used to measure a parameter most representative of total local blood flow, and light of a very much shorter wavelength, probably green light, would allow more confidence in estimates of true capillary perfusion. Because the commonly used visible red light can, but does not necessarily detect deep AVA perfusion, the influence depending upon the magnitude of the AVA perfusion, measurements by an instrument based on such red light is difficult to define.

Human circulatory and thermoregulatory adaptations with heat acclimation and exercise in a hot, dry environment.

1. Heat acclimation was induced in eight subjects by asking them to exercise until exhaustion at 60% of maximum oxygen consumption rate (VO2) for 9-12 consecutive days at an ambient temperature of 40 degrees C, with 10% relative humidity (RH). Five control subjects exercised similarly in a cool environment, 20 degrees C, for 90 min for 9-12 days; of these, three were exposed to exercise at 40 degrees C on the first and last day. 2. Acclimation had occurred as seen by the increased average endurance from 48 min to 80 min, the lower rate of rise in the heart rate (HR) and core temperature and the increased sweating. 3. Cardiac output increased significantly from the first to the final heat exposure from 19.6 to 21.4 l min-1; this was possibly due to an increased plasma volume and stroke volume. 4. The mechanism for the increased plasma volume may be an isosmotic volume expansion caused by influx of protein to the vascular compartment, and a sodium retention induced by a significant increase in aldosterone. 5. The exhaustion coincided with, or was elicited when, core temperature reached 39.7 +/- 0.15 degrees C; with progressing acclimation processes it took progressively longer to reach this level. However, at this point we found no reduction in cardiac output, muscle (leg) blood flow, no changes in substrate utilization or availability, and no recognized accumulated 'fatigue' substances. 6. It is concluded that the high core temperature per se, and not circulatory failure, is the critical factor for the exhaustion during exercise in heat stress.

Observations on a new non-invasive monitor of skin blood flow.

1. A 'tissue perfusion monitor' (TPM) to non-invasively provide an index of skin blood flow (SkBF) has been developed; it employs photoelectric plethysmographic principles to measure changes in the nett flux of red blood cells in superficial microvasculature. 2. The 'tissue perfusion index' (TPI) varies in proportion to SkBF, provided local haemoglobin concentration does not change significantly. TPI of humans and experimental animals has been shown to indicate reliably, well established phenomena such as decreased SkBF in response to mechanical restriction, cold or Valsalva's manoeuvre, or increased SkBF in response to heat, acetylcholine, sodium nitrite or local nerve blockade. 3. SkBF in sheep was varied between 1 and 156 mL/100g per min as measured with radioactive microspheres. Simultaneous measurements were made using the TPM and four laser-Doppler instruments. The TPI yielded a correlation coefficient of 0.938, and when data were expressed as percentage change, the regression line did not differ significantly from the line of identity and the root-mean-square-error was 6.2%. Data for the laser-Doppler indices of SkBF were, respectively, 0.549-0.786, highly significant deviations in slopes, and 13.6-16.7%. 4. Thus, the TPI is a reliable index of changes in SkBF. Compared with some other available instruments, the TPM is more precise; it is also less sensitive to movement artefact, can be completely portable by battery operation, probes can be multiplexed to a single meter and it is likely to be much less expensive than current lasers. 5. Applications include, for example, experimental investigations of SkBF in man and animals, clinical uses such as evaluation of the efficacy of regional nerve blockade or of circulatory restitution after reconstructive surgery, and clinical tests of neurovascular function.

The effects of prostacyclin and thromboxane analogue (U46619) on the fetal circulation and umbilical flow velocity waveforms.

In placental insufficiency and pre-eclampsia the relative production rates of prostacyclin and thromboxane by the placenta and umbilical vessels are altered and the Doppler umbilical flow velocity waveform shows a high resistance pattern. To investigate the control of umbilical placental blood flow by those eicosanoids either prostacyclin (10 micrograms/min), or the thromboxane analogue U46619 (10 ng/min) was infused into the distal aorta of 12 chronically catheterized fetal lambs at day 125. Thromboxane produced a rise in mean arterial pressure and a rise in the systolic diastolic ratio of the umbilical artery flow waveform (2.6 to 3.1; P less than 0.05). Umbilical blood flow did not change and there was no evidence of altered flow to other organs. Prostacyclin caused a fall in fetal mean arterial pressure and a decrease in the umbilical artery systolic diastolic ratio (2.9 to 2.4; P less than 0.05). Prostacyclin produced a three-fold increase in lung perfusion (and the onset of fetal breathing movements) and this was associated with a 90% reduction in muscle blood flow (hindlimb muscle flow reduced from 12.5 to 1.1 ml.min-1 100g-1; P less than 0.01). We conclude that the local release of thromboxane in the fetal placental vascular bed could account for the rise in systolic diastolic ratio seen in umbilical placental insufficiency.

Circulatory effects of a depilatory dose of mouse epidermal growth factor in sheep.

1. Haemodynamic parameters and tissue blood flow rates were measured in two groups of five sheep infused I.V. for 24 h with either saline or 128.6 micrograms mouse epidermal growth factor (mEGF) kg-1 body weight. Measurements were made preinfusion and at +3, +12, +24, +27 and +48 h. We wished to assess relationships between blood flow rates and known functional changes in various organs during EGF treatment, especially any relationship between skin blood flow rate and the known depilatory effects of the protein in sheep. 2. Cardiac output increased and total peripheral resistance and mean arterial pressure decreased during and after infusion in the mEGF-treated group relative to the control group. 3. The greatest increase in blood flow rates occurred in woolled skin (+500%) during mEGF infusion, a result which in itself may have been disparate with the known depilatory effects of EGF. The mucosas of the alimentary tract (except abomasum) and the submaxillary and sublingual salivary glands also showed vasodilatation. 4. There were short-term increases in pituitary and adrenal gland blood flow that may have been associated with the corticotrophin-releasing factor properties of EGF. Flow in the thyroids showed the greatest increase post-infusion when thyroid hormone metabolism may have been reverting to normal. Blood flow rates decreased in the pancreas and perirenal fat. 5. Our general conclusion was that mEGF had specific vasodilator effects in the skin, the thyroid, submaxillary and sublingual glands and the mucosas of most of the alimentary tract.

Fever and regional blood flows in wethers and parturient ewes.

To determine whether the reported absence of fever in full-term-pregnant ewes might be associated with shifts of regional blood flows from thermogenic tissues to placenta during this critical period, fevers were induced twice by injections of Escherichia coli lipopolysaccharide (LPS, 0.25 microgram/kg iv) into each of six Merino ewes from 8 to 1 days prepartum, and their regional blood flow distribution was measured with radioactive, 15-microns-diam microspheres before and during the rise in fever (when their rectal temperature had risen approximately 0.4 degree C). Unexpectedly, fever always developed, rising to heights not significantly different at any time before parturition [4-8 days prepartum = 0.81 +/- 0.23 degree C (SE); 1-3 days prepartum = 0.75 +/- 0.17 degree C) and similar to those in three wethers treated similarly (0.90 +/- 0.10 degree C). Generally, during rising fever, blood flow in the ewes shifted away from heat loss tissues (e.g., skin, nose) to heat production tissues (e.g., shivering muscle, fat) and cardiac output increased; blood flow through redistribution organs (e.g., splanchnic bed) decreased. The reverse occurred during defervescence. Utero-placental blood flow remained high in the febrile ewes. These regional blood flow distributions during febrigenesis and lysis are essentially the same as those during exposures to ambient cold and heat, respectively. Some differences in the responses of cardiac output and its redistribution, however, were apparent between wethers and pregnant ewes. We conclude that 1) the previously reported "absence of fever in the full-term-pregnant sheep" should not be regarded as a general phenomenon and 2) full-term-pregnant sheep support fever production without sacrificing placental blood flow.