Training effects on regional blood flow response to maximal exercise in foxhounds

The effect of training on the regional blood flow response to maximal exercise was investigated in the foxhound. Training consisted of 8-12 wk of treadmill running at 80% of maximal heart rate 1 h/day for 5 days/wk and resulted in a 31% increase in maximal O2 consumption, a 28% increase in maximal cardiac output, and a 23% decrease in systemic vascular resistance during maximal exercise. Blood flow to the heart, diaphragm, brain, skin, and 9 of 10 muscles investigated was similar during maximal exercise pre- and posttraining; however, blood flow to the gastrocnemius muscle was greater posttraining than it was pretraining. Blood flow to the stomach, small intestine, and pancreas decreased during maximal exercise pre- and posttraining; however, blood flow to the large intestine, spleen, liver, adrenal glands, and kidneys decreased during maximal exercise only posttraining. In addition, a larger decrease in blood flow to the stomach during maximal exercise was found posttraining compared with pretraining. These results demonstrate that blood flow to skeletal muscle, the kidneys, and the splanchnic region of the foxhound during maximal exercise can be significantly altered by dynamic exercise training.     

Plasma lactate concentration and muscle blood flow during dynamic exercise with negative-pressure breathing.

This study assessed the hypothesis that increasing cardiac filling pressure (CFP) would enhance contracting muscle blood flow (MBF) by stretching cardiopulmonary baroreceptors and attenuate the increase in plasma lactate concentration ([Lac(-)](p)) during dynamic exercise. Continuous negative-pressure breathing (CNPB) (-15 cmH(2)O) was used to increase the CFP by accelerating the venous return to the heart. In the first series of experiments, 10 men performed a graded exercise seated on a cycle ergometer with (N1) and without CNPB (C1). The increase in [Lac(-)](p) for N1 was attenuated at 60%, 90%, and 100% of maximal exercise intensity compared with that in C1 (P < 0.001). Also, the increases in mean arterial pressure (MAP) and plasma catecholamine concentrations were attenuated in N1 compared with those in C1 throughout the graded exercise (P < 0.05). However, heart rate and pulse pressure were not significantly influenced by CNPB. Second, we studied the impact of CNPB on forearm MBF during a rhythmic handgrip exercise in 5 of the 10 subjects. Forearm MBF was measured immediately after cessation of the exercise by venous occlusion plethysmography at rest, 30%, 50%, and 70% of maximal work load (WL(max)) with (N2) and without CNPB (C2). Forearm MBF and vascular conductance for both trials increased with the increase in intensity, but forearm skin blood flow measured by laser-Doppler flowmetry remained unchanged. MBF and vascular conductance in N2, however, increased more than in C2 at every intensity (P < 0.01) except for MBF at 70% WL(max), whereas the increase in MAP for N2 was attenuated compared with that in C2 (P < 0.05). Thus augmented active muscle vasodilation occurred in N2 with a lower increase in MAP compared with that in C2. These findings suggest that the stretch of intrathoracic baroreceptors, such as cardiopulmonary mechanoreceptors, by CNPB increased MBF by suppressing sympathetic nerve activity. The attenuation of the increase in [Lac(-)](p) might be caused, at least partially, by the increased MBF.     

Effects of high-intensity sprint training on skeletal muscle blood flow in rats.

The regional blood flow response (via radioactive microspheres) was determined for female rats after 6 wk of high-intensity sprint training (HIST) or limited cage activity as the animals exercised at work loads that would elicit maximal O2 uptake. Blood flow to the different organs of the abdominal region was greatly reduced during maximal exercise conditions, and the magnitude of the reduction appeared to be similar for both the HIST group of rats and their sedentary (SED) control counterparts. Of the 20 different hindlimb muscles examined in the present study, blood flow to the soleus, plantaris, gastrocnemius, flexor hallicus longus, vastus lateralis, rectus femoris, biceps femoris, and adductor magnus and brevis muscles was significantly greater (P less than 0.05) in the HIST rats during maximal exercise conditions than in the SED control rats. Correspondingly, blood flow to the total hindlimb during maximal exercise was also significantly greater in the HIST rats than in the SED control rats [240 +/- 18 vs. 192 +/- 15 (SE) ml.min-1.100 g-1]. These results support the contention that the increase in maximal cardiac output that is produced by HIST in the rat is primarily directed toward the working skeletal muscle and not toward the organs found in the abdominal region. We conclude from these experiments that HIST will produce significant adaptations in central cardiac function and skeletal muscle blood flow in the rat.     

Oxygen transport and peripheral microcirculation in long-term diabetes

The purpose of this investigation was to evaluate the impact of long-term diabetes on muscle blood flow (MBF) and oxygen transport (vO2) during exercise. Twelve male patients (58 +/- 8 years, mean +/- SD), with at least a 10-year history of diabetes controlled by insulin, and seven age-matched controls (56 +/- 5 years, mean +/- SD) participated in this study. No patient had been clinically diagnosed as having peripheral vascular disease, and on the average resting ankle/arm systolic blood pressure ratios were normal. Following a baseline period, 5 min of cycle ergometer exercises at 75 W were performed in the upright position and, after 1-hr recovery, in the supine position. Continuous vO2 was determined via breath-by-breath analysis. MBF was measured in the vastus lateralis (VL) and tibialis anterior (TA) by 133Xe clearance. In the erect position, the diabetic group (compared with the control group, respectively) exhibited significantly (P less than 0.05) lower exercise MBF [ml. (100 g.min)-1] in both VL (19 +/- 2.5 vs 30.9 +/- 2) and TA (13.7 +/- 2 vs 22.0 +/- 4), a lower steady-state VO2 (1.3 +/- 0.3 vs 1.7 +/- 0.2 liters.min-1) during exercise including the values in the last 15 sec of exercise, and greater accumulation of blood lactate (35 +/- 2 vs 22.0 +/- 2 mg/100 ml). The same trends in the data were observed during supine exercise; however, the blood pressure of the diabetics was significantly elevated during exercise when compared with that of controls. The reduced exercise MBF in the TA and VL demonstrated that impaired microvascular flow, without clinically overt peripheral vascular disease, in long-term diabetics leads to reduced oxygen delivery and exercise tolerance.     

Effect of contraction frequency on leg blood flow during knee extension exercise in humans.

Previous studies in isolated muscle preparations have shown that muscle blood flow becomes compromised at higher contraction frequencies. The purpose of this study was to examine the effect of increases in contraction frequency and muscle tension on mean blood flow (MBF) during voluntary exercise in humans. Nine male subjects [23.6 +/- 3.7 (SD) yr] performed incremental knee extension exercise to exhaustion in the supine position at three contraction frequencies [40, 60, and 80 contractions/min (cpm)]. Mean blood velocity of the femoral artery was determined beat by beat using Doppler ultrasound. MBF was calculated by using the diameter of the femoral artery determined at rest using echo Doppler ultrasound. The work rate (WR) achieved at exhaustion was decreased (P < 0.05) as contraction frequency increased (40 cpm, 16.2 +/- 1.4 W; 60 cpm, 14.8 +/- 1.4 W; 80 cpm, 13.2 +/- 1.3 W). MBF was similar across the contraction frequencies at rest and during the first WR stage but was higher (P < 0.05) at 40 than 80 cpm at exercise intensities >5 W. MBF was similar among contraction frequencies at exhaustion. In humans performing knee extension exercise in the supine position, muscle contraction frequency and/or muscle tension development may appreciably affect both the MBF and the amplitude of the contraction-to-contraction oscillations in muscle blood flow.     

Cardiovascular and thermoregulatory responses to repeated anticholinesterase administration

1. 1.|Pyridostigmine administration decreased resting heart rate by 11 ± 7 beats/min and resting oesophageal temperature by 0.23 ± 12°C after 50 h (P < 0.05). In addition, red blood cell cholinesterase activity was decreased an average of 43 ± 7% after 50 h of pyridostigmine treatment.

2. 2.|The lower heart rates and core temperatures at rest were continued during high intensity exercise in a 35°C environment. Whole body sweating was 12 ± 18% higher (P = 0.20) during exercise in the heat after 50 h of pyridostigmine treatment.

3. 3.|Repeated anticholinesterase administration had little effect on cardiovascular and thermoregulatory responses during high intensity exercise.

Muscular blood flow in human highlanders and in lowlanders living at altitude (3 800 m) (author's transl)]

Muscular blood flow (MBF) was measured in the tibialis anteiror muscle by the 133Xe washout technique. Measurements were made in lowlanders at sea level, in native highlanders at 3 800 m and in lowlanders who had been living at this altitude for less than 6 months. At rest and during exercise, MBF is smaller in highlanders and in the high altitude visitors than in lowlanders. If, instead of total blood flow, the red cell flow is calculated (by multiplying MBF by the haematocrit) these differences are no longer significant at rest and are minimized during exercice. These results are consistent with reduction of cardiac output and blood supply to other regions in subjects who are acclimatized to altitude.     

Biosynthesis and properties of an extracellular metalloprotease from the Antarctic marine bacterium Sphingomonas paucimobilis

An extracellular protease from the marine bacterium Sphingomonas paucimobilis, strain 116, isolated from the stomach of Antarctic krill, Euphausia superba Dana, was purified and characterized. The excretion of protease was maximal at temperatures from 5 to 10°C, i.e. below the temperature optimum for the strain growth (15°C). The highly purified enzyme was a metalloprotease [sensivity to ethylenediaminetetraacetic acid (EDTA)] and showed maximal activity against proteins at 20–30°C and pH 6.5–7.0, and towards N-benzoyl-tyrosine ethyl ester (BzTyrOEt) at pH 8.0. At 0°C the enzyme retained as much as 47% of maximal activity in hydrolysis of urea denatured haemoglobin (Hb) (at pH 7.0), and at −5 and −10°C, 37 and 30%, respectively. The metalloprotease was stable up to 30°C for 15 min and up to 20°C for 60 min. These results indicate that the proteinase from S. paucimobilis 116 is a cold-adapted enzyme.     

Muscle metaboreflex-induced increases in cardiac sympathetic activity vasoconstrict the coronary vasculature.

Ischemia of active skeletal muscle evokes a powerful blood pressure-raising reflex termed the muscle metaboreflex (MMR). MMR activation increases cardiac sympathetic nerve activity, which increases heart rate, ventricular contractility, and cardiac output (CO). However, despite the marked increase in ventricular work, no coronary vasodilation occurs. Using conscious, chronically instrumented dogs, we observed MMR-induced changes in arterial pressure, CO, left circumflex coronary blood flow (CBF), and coronary vascular conductance (CVC) before and after alpha1-receptor blockade (prazosin, 100 microg/kg iv). MMR was activated during mild treadmill exercise by partially reducing hindlimb blood flow. In control experiments, MMR activation caused a substantial pressor response-mediated via increases in CO. Although CBF increased (+28.1 +/- 3.7 ml/min; P < 0.05), CVC did not change (0.45 +/- 0.05 vs. 0.47 +/- 0.06 ml x min(-1) x mmHg(-1), exercise vs. exercise with MMR activation, respectively; P > 0.05). Thus all of the increase in CBF was due to the increase in arterial pressure. In contrast, after prazosin, MMR activation caused a greater increase in CBF (+55.9 +/- 17.1 ml/min; P < 0.05 vs. control) and CVC rose significantly (0.59 +/- 0.08 vs. 0.81 +/- 0.17 ml x min(-1) x mmHg(-1), exercise vs. exercise with MMR activation, respectively; P < 0.05). A greater increase in CO also occurred (+2.01 +/- 0.1 vs. +3.27 +/- 1.1 l/min, control vs. prazosin, respectively; P < 0.05). We conclude that the MMR-induced increases in sympathetic activity to the heart functionally restrain coronary vasodilation, which may limit increases in ventricular function.     

Distribution of blood flow during exercise after blood volume expansion in swine

To study the distribution of blood flow after blood volume expansion, seven miniature swine ran at high speed (17.6-20 km/h, estimated to require 115% of maximal O2 uptake) on a motor-driven treadmill on two occasions: once during normovolemia and once after an acute 15% blood volume expansion (homologous whole blood). O2 uptake, cardiac output, heart rate, mean arterial pressure, and distribution of blood flow (with radiolabeled microspheres) were measured at the same time during each of the exercise bouts. Maximal heart rate was identical between conditions (mean 266); mean arterial pressure was elevated during the hypovolemic exercise (149 +/- 5 vs. 137 +/- 6 mmHg). Although cardiac output was higher and arterial O2 saturation was maintained during the hypervolemic condition (10.5 +/- 0.7 vs. 9.3 +/- 0.6 l/min), O2 uptake was not different (1.74 +/- 0.08 vs. 1.74 +/- 0.09 l/min). Mean blood flows to cardiac (+12.9%), locomotory (+9.8%), and respiratory (+7.5%) muscles were all elevated during hypervolemic exercise, while visceral and brain blood flows were unchanged. Calculated resistances to flow in skeletal and cardiac muscle were not different between conditions. Under the experimental conditions of this study, O2 uptake in the miniature swine was limited at the level of the muscles during hypervolemic exercise. The results also indicate that neither intrinsic contractile properties of the heart nor coronary blood flow limits myocardial performance during normovolemic exercise, because both the pumping capacity of the heart and the coronary blood flow were elevated in the hypervolemic condition.     

Systemic hemodynamics and renal function in hemorrhaged dogs resuscitated with cross-linked hemoglobin

Cross-linked hemoglobin (XL-Hb) infused into dogs increases mean arterial pressure (MAP) but decreases blood flow to the renal (RBF), mesenteric (MBF), and iliac (IBF) circulations. These actions differ markedly from dextran infusion (which increases RBF, MBF, and IBF without altering MAP) and may be due to scavenging of nitric oxide by XL-Hb. However, because the hormonal milieu regulating regional circulation is altered during hemorrhage (when XL-Hb may be used), we studied whether systemic hemodynamics, RBF, MBF, IBF, and renal excretory function in hemorrhaged dogs was altered when resuscitated with XL-Hb compared with dextran (n = 6 each). Hemorrhage decreased MAP by 25% due to a 75% decline in cardiac output. RBF, MBF, and IBF all fell by 33, 64, and 72%, respectively (P<0.05 each). There was also a fall in glomerular filtration rate (GFR), urinary flow, and sodium excretion (P<0.05 each). After resuscitation, MAP, cardiac output, RBF, MBF, IBF, and GFR all recovered to basal values with either XL-Hb or dextran. Urinary flow and sodium excretion increased to above basal levels with dextran (both by 3.5-fold; P<0.05) or XL-Hb (by 7.5- and 10-fold, respectively; P<0.05). We conclude that resuscitation with XL-Hb after hemorrhage not only increases MAP, but also restores RBF, MBF, IBF, GFR, and urinary sodium and volume excretion analogously to dextran. The results contrast with those in normal dogs and suggest that nitric oxide inhibition does not impair hemodynamic and renal function recovery during hemorrhage.     

Critical thermal maximum and body water loss in first instar larvae of three Cetoniidae species (Coleoptera)

Critical thermal maximum (CT_max) and body water losses were measured in first instar larvae of Gnorimus nobilis, Osmoderma eremita (Trichiinae) and Cetonischema aeruginosa (Cetoniinae) when air temperature was increased gradually (0.5 °C/min) from 20 °C to the critical thermal maximum (CT_max), in dry air (near 0% R.H.).

The CT_max was significantly lower in O. eremita (45.6±0.7 °C) than in G. nobilis (48.5±0.6) and C. aeruginosa (51.4±0.9 °C).

An increase of 10 °C (30–40 °C) induced a 2-fold increase of the water loss in C. aeruginosa and O. eremita (Q₁₀=2.10±0.12 and 2.13±0.20, respectively). In the range from 40 to 45 °C to CT_max a strong increase of the water loss was observed in O. eremita and C. aeruginosa, respectively. Body water losses were significantly lower in C. aeruginosa than in O. eremita and G. nobilis over the range 20 °C—CT_max; no significant difference occurred between G. nobilis and O. eremita.     

Inspiratory and expiratory muscle perfusion in maximally exercised ponies

The present study was carried out on seven healthy ponies to examine the extent of blood flow in various inspiratory and expiratory muscles at rest and during maximal exertion as well as to determine the proportion of cardiac output needed to perfuse respiratory muscles during these conditions. Tissue blood flow was studied with 15 micron-diameter radionuclide-labeled microspheres injected into the left ventricle during steady conditions. The inspiratory and expiratory muscles comprised 2.41 and 3.05% of body weight, respectively, and received 6.17 and 3.75% of the cardiac output at rest. With maximal exercise, heart rate (from 55 +/- 3 to 218 +/- 4 beats/min), mean aortic pressure (from 125 +/- 5 to 170 +/- 6 mmHg), and cardiac output (from 96 +/- 11 to 730 +/- 78 ml.min-1.kg-1) increased markedly. During exercise blood flow increased significantly in all respiratory muscles (P less than 0.0001) as vascular resistance decreased precipitously. Marked heterogeneity of perfusion existed among various inspiratory as well as expiratory muscles during exercise. Among the inspiratory muscles, the highest perfusion occurred in the diaphragm followed by serratus ventralis, and among the expiratory muscles, the highest perfusion occurred in the internal oblique abdominis and the transverse thoracis (triangularis sterni). Collectively, the inspiratory (8.44%) and expiratory (6.35%) muscle blood flow comprised 14.8 +/- 1.2% of the cardiac output during maximal exercise, a significant increase above resting value, whereas renal fraction of cardiac output decreased from 21% (at rest) to 0.72%.     

Regional muscle blood flow capacity and exercise hyperemia in high-intensity trained rats

The purpose of this study was to determine the effects of high-intensity treadmill exercise training on 1) the regional distribution of muscle blood flow within and among muscles in rats during high-intensity treadmill exercise (phase I) and 2) on the total and regional hindlimb skeletal muscle blood flow capacities as measured in isolated perfused rat hindquarters during maximal papaverine vasodilation (phase II). Two groups of male Sprague-Dawley rats were trained 5 days/wk for 6 wk with a program consisting of 6 bouts/day of 2.5-min runs at 60 m/min up a 15% grade with 4.5-min rest periods between bouts. After training, blood flows were measured with the radiolabeled microsphere technique (phase I) in pair-weighted sedentary control and exercise-trained rats while they ran at 60 m/min (0% grade). In phase II of the study, regional vascular flow capacities were determined at three perfusion pressures (30, 40, and 50 mmHg) in isolated perfused hindquarters of control and trained rats maximally vasodilated with papaverine. The results indicate that this exercise training program produces increases in the vascular flow capacity of fast-twitch glycolytic muscle tissue of rats. However, these changes were not apparent in the magnitude or distribution of muscle blood flow in conscious rats running at 60 m/min, since blood flows within and among muscles during exercise were the same in trained and control rats.     

Gastrointestinal blood flow and postprandial metabolism in swimming sea bass Dicentrarchus labrax

In trout and salmon, the metabolic costs of exercise and feeding are additive, which would suggest that gastrointestinal blood flow during exercise is maintained to preserve digestive and absorptive processes related to the specific dynamic action (SDA) of food. However, in most published studies, gastrointestinal blood flow drops during swimming, hypoxia, and general stress. To test whether gastrointestinal blood flow is spared during exercise after feeding, sea bass were instrumented with flow probes to measure cardiac output and celiacomesenteric blood flow while swimming in a respirometer before and after feeding. Swimming at 2 body lengths per second (bl s(-1)) increased metabolic rate considerably more than did feeding (208% vs. 32% increase, respectively, relative to resting), and a similar pattern was observed for cardiac output. In unfed fish, resting gastrointestinal blood flow was 13.8+/-0.5 mL min(-1) kg(-1). After feeding, resting gastrointestinal blood flow increased by 82% but then decreased progressively with increasing swimming speeds. At 2 bl s(-1), gastrointestinal blood flow in fed fish was not significantly different compared with that in unfed swimming fish, and, therefore, the data do not support the gastrointestinal sparing hypothesis. The magnitude of the SDA was maintained despite the decrease in gastrointestinal blood flow and the consequent reduction in oxygen supply to the gut. An estimate of maximal oxygen flow to the gastrointestinal tract after feeding yielded 2.6 mmol O(2) h(-1) kg(-1), but this amount is not able to cover the oxygen demand of 3.16 mmol O(2) h(-1) kg(-1). Therefore, the SDA must reflect metabolic processes in tissues other than those directly perfused by the celiacomesenteric artery.     

Cardiac output and muscle blood flow during rest-associated apneas of elephant seals

In order to evaluate hemodynamics and blood flow during rest-associated apnea in young elephant seals (Mirounga angustirostris), cardiac outputs (CO, thermodilution), heart rates (HR), and muscle blood flow (MBF, laser Doppler flowmetry) were measured. Mean apneic COs and HRs of three seals were 46% and 39% less than eupneic values, respectively (2.1+/-0.3 vs. 4.0+/-0.1 mL kg(-1) s(-1), and 54+/-6 vs. 89+/-14 beats min(-1)). The mean apneic stroke volume (SV) was not significantly different from the eupneic value (2.3+/-0.2 vs. 2.7+/-0.5 mL kg(-1)). Mean apneic MBF of three seals was 51% of the eupneic value. The decline in MBF during apnea was gradual, and variable in both rate and magnitude. In contrast to values previously documented in seals during forced submersions (FS), CO and SV during rest-associated apneas were maintained at levels characteristic of previously published values in similarly-sized terrestrial mammals at rest. Apneic COs of such magnitude and incomplete muscle ischemia during the apnea suggest that (1) most organs are not ischemic during rest-associated apneas, (2) the blood O(2) depletion rate is greater during rest-associated apneas than during FS, and (3) the blood O(2) store is not completely isolated from muscle during rest-associated apneas.     

Altered muscle metaboreflex control of coronary blood flow and ventricular function in heart failure

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF), coronary vascular conductance (CVC), and regional left ventricular performance in conscious, chronically instrumented dogs during treadmill exercise before and after the induction of heart failure (HF). In control experiments, muscle metaboreflex activation during mild exercise elicited significant reflex increases in mean arterial pressure, heart rate, and cardiac output. CBF increased significantly, whereas no significant change in CVC occurred. There was no significant change in the minimal rate of myocardial shortening (-dl/dt(min)) with muscle metaboreflex activation during mild exercise (15.5 +/- 1.3 to 16.8 +/- 2.4 mm/s, P > 0.05); however, the maximal rate of myocardial relaxation (+dl/dt(max)) increased (from 26.3 +/- 4.0 to 33.7 +/- 5.7 mm/s, P < 0.05). Similar hemodynamic responses were observed with metaboreflex activation during moderate exercise, except there were significant changes in both -dl/dt(min) and dl/dt(max). In contrast, during mild exercise with metaboreflex activation during HF, no significant increase in cardiac output occurred, despite a significant increase in heart rate, inasmuch as a significant decrease in stroke volume occurred as well. The increases in mean arterial pressure and CBF were attenuated, and a significant reduction in CVC was observed (0.74 +/- 0.14 vs. 0.62 +/- 0.12 ml x min(-1) x mmHg(-1); P < 0.05). Similar results were observed during moderate exercise in HF. Muscle metaboreflex activation did not elicit significant changes in either -dl/dt(min) or +dl/dt(max) during mild exercise in HF. We conclude that during HF the elevated muscle metaboreflex-induced increases in sympathetic tone to the heart functionally vasoconstrict the coronary vasculature, which may limit increases in myocardial performance.     

Muscle contraction-blood flow interactions during upright knee extension exercise in humans.

To test for evidence of a muscle pump effect during steady-state upright submaximal knee extension exercise, seven male subjects performed seven discontinuous, incremental exercise stages (3 min/stage) at 40 contractions/min, at work rates ranging to 60-75% peak aerobic work rate. Cardiac cycle-averaged muscle blood flow (MBF) responses and contraction-averaged blood flow responses were calculated from continuous Doppler sonography of the femoral artery. Net contribution of the muscle pump was estimated by the difference between mean exercise blood flow (MBFM) and early recovery blood flow (MBFR). MBFM rose in proportion with increases in power output with no significant difference between the two methods of calculating MBF. For stages 1 and 5, MBFM was greater than MBFR; for all others, MBFM was similar to MBFR. For the lighter work rates (stages 1-4), there was no significant difference between exercise and early recovery mean arterial pressure (MAP). During stages 5-7, MAP was significantly higher during exercise and fell significantly early in recovery. From these results we conclude that 1) at the lightest work rate, the muscle pump had a net positive effect on MBFM, 2) during steady-state moderate exercise (stages 2-4) the net effect of rhythmic muscle contraction was neutral (i.e., the impedance due to muscle contraction was exactly offset by the potential enhancement during relaxation), and 3) at the three higher work rates tested (stages 5-7), any enhancement to flow during relaxation was insufficient to fully compensate for the contraction-induced impedance to muscle perfusion. This necessitated a higher MAP to achieve the MBFM.     

Comparative effects of vasopressin, norepinephrine, and L-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Norepinephrine (NE), a standard of care, AVP, an alternative candidate, and L-canavanine (LC), a selective inhibitor of inducible nitric oxide synthase, were compared for efficacy and innocuousness on global and regional hemodynamics, plasmatic and tissue lactate-to-pyruvate ratio (L/P), tissue high-energy phosphates, renal function, and tissue capillary permeability in a rat model of endotoxic normokinetic shock. Mean arterial pressure (MAP) decreased ( approximately 35%) but aortic blood flow increased during endotoxin infusion (P < 0.05 vs. control). Additionally, there was a decrease in mesenteric (MBF) and renal (RBF) blood flows along with regional-to-systemic ratio (P < 0.05 vs. control). All tested drugs restored MAP to basal levels but slightly decreased abdominal aortic flow; however, RBF and MBF remained unchanged. Endotoxin significantly decreased diuresis and inulin clearance ( approximately 3- to 4-fold), whereas AVP or LC attenuated this drop (P < 0.05 vs. control). In contrast, NE did not improve endotoxin-induced renal dysfunction. Endotoxin induced gut and lung hyperpermeability (P < 0.05 vs. control). Endotoxin-induced gut hyperpermeability was inhibited by AVP, LC, and NE. Endotoxin-induced lung hyperpermeability was further worsened by NE ( approximately 2-fold increase) but not AVP infusion (P < 0.05 vs. endotoxin). LC significantly improved endotoxin-induced pulmonary hyperpermeability. Endotoxin increased renal lactate and decreased renal ATP. NE did not change renal lactate or renal ATP. AVP and LC decreased renal lactate and normalized renal ATP. Finally, endotoxin was associated with increased lactate levels and L/P ( approximately 2- and 1.5-fold increases vs. control, respectively), whereas AVP and LC, but not NE, normalized both parameters after endotoxin challenge. These results suggest that, in a short-term endotoxic shock model, AVP improves systemic hemodynamics without side effects and has particular beneficial effects on renal function.     

Temperature-dependence of cardiac output and regional blood flow in rainbow trout, Salmo gairdneri Richardson

Cardiac output, blood flow distribution and regional perfusion were determined in free-swimming rainbow trout acclimated to 6, 12 and 18°C, using the indicator dilution and microsphere methods. Cardiac output (ml min⁻¹ kg⁻¹) increased linearly with increasing temperature, while circulation time decreased. Blood flow distribution (% of cardiac output) to the spleen, liver, kidney, gall bladder and gastro-intestinal tract was significantly reduced at 18°C relative to 6°C-acclimated fish. White muscle received the largest fraction of cardiac output, and blood flow distribution to white muscle increased significantly with increasing acclimation temperature. Blood perfusion (ml h⁻¹ g⁻¹) of various organs and red muscle was not influenced by acclimation temperature, while white muscle perfusion increased with increasing temperature. These results demonstrate physiological adaptation of the cardiovascular system of rainbow trout to changes in acclimation temperature.