Role of L-selectin in physiological manifestations after burn and smoke inhalation injury in sheep.
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The effects of a monoclonal antibody against L-selectin [leukocyte adhesion molecule (LAM)1-3] on microvascular fluid flux were determined in conscious sheep subjected to a combined injury of 40% third-degree burn and smoke inhalation. This combined injury induced a rapid increase in systemic prefemoral lymph flow (sQlymph) from the burned area and a delayed-onset increase in lung lymph flow. The initial increase in sQlymph was associated with an elevation of the lymph-to-plasma oncotic pressure ratio; consequently, it leads to a predominant increase in the systemic soft tissue permeability index (sPI). In an untreated control group, the increased sPI was sustained beyond 24 h after injury. Pretreatment with LAM1-3 resulted in earlier recovery from the increased sPI, although the initial responses in sQlymph and sPI were identical to those in the nontreatment group. The delayed-onset lung permeability changes were significantly attenuated by pretreatment with LAM1-3. These findings indicate that both leukocyte-dependent and -independent mechanisms are involved in the pathogenesis that occurs after combined injury with burn and smoke inhalation. (+info)
Mechanisms of acute cardiovascular response to periodic apneas in sedated pigs.
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This study was designed to evaluate the importance of sympathoadrenal activation in the acute cardiovascular response to apneas and the role of hypoxemia in this response. In addition, we evaluated the contribution of the vagus nerve to apnea responses after chemical sympathectomy. In six pigs preinstrumented with an electromagnetic flow probe and five nonpreinstrumented pigs, effects of periodic nonobstructive apneas were tested under the following six conditions: room air breathing, 100% O2 supplementation, both repeated after administration of hexamethonium (Hex), and both repeated again after bilateral vagotomy in addition to Hex. With room air apneas, during the apnea cycle, there were increases in mean arterial pressure (MAP; from baseline of 108 +/- 4 to 124 +/- 6 Torr, P < 0.01), plasma norepinephrine (from 681 +/- 99 to 1,825 +/- 578 pg/ml, P < 0.05), and epinephrine (from 191 +/- 67 to 1,245 +/- 685 pg/ml, P < 0.05) but decreases in cardiac output (CO; from 3.3 +/- 0.6 to 2.4 +/- 0.3 l/min, P < 0.01) and cervical sympathetic nerve activity. With O2 supplementation relative to baseline, apneas were associated with small increases in MAP (from 112 +/- 4 to 118 +/- 3 Torr, P < 0.01) and norepinephrine (from 675 +/- 97 to 861 +/- 170 pg/ml, P < 0.05). After Hex, apneas with room air were associated with small increases in MAP (from 103 +/- 6 to 109 +/- 6 Torr, P < 0.05) and epinephrine (from 136 +/- 45 to 666 +/- 467 pg/ml, P < 0.05) and decreases in CO (from 3.6 +/- 0.4 to 3.2 +/- 0. 5 l/min, P < 0.05). After Hex, apneas with O2 supplementation were associated with decreased MAP (from 107 +/- 5 to 100 +/- 5 Torr, P < 0.05) and no other changes. After vagotomy + Hex, with room air and O2 supplementation, apneas were associated with decreased MAP (from 98 +/- 6 to 76 +/- 7 and from 103 +/- 7 to 95 +/- 6 Torr, respectively, both P < 0.01) but increased CO [from 2.7 +/- 0.3 to 3. 2 +/- 0.4 l/min (P < 0.05) and from 2.4 +/- 0.2 to 2.7 +/- 0.2 l/min (P < 0.01), respectively]. We conclude that sympathoadrenal activation is the major pressor mechanism during apneas. Cervical sympathetic nerve activity does not reflect overall sympathoadrenal activity during apneas. Hypoxemia is an important but not the sole trigger factor for sympathoadrenal activation. There is an important vagally mediated reflex that contributes to the pressor response to apneas. (+info)
Compensatory alveolar growth normalizes gas-exchange function in immature dogs after pneumonectomy.
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To determine the extent and sources of adaptive response in gas-exchange to major lung resection during somatic maturation, immature male foxhounds underwent right pneumonectomy (R-Pnx, n = 5) or right thoracotomy without pneumonectomy (Sham, n = 6) at 2 mo of age. One year after surgery, exercise capacity and pulmonary gas-exchange were determined during treadmill exercise. Lung diffusing capacity (DL) and cardiac output were measured by a rebreathing technique. In animals after R-Pnx, maximal O2 uptake, lung volume, arterial blood gases, and DL during exercise were completely normal. Postmortem morphometric analysis 18 mo after R-Pnx (n = 3) showed a vigorous compensatory increase in alveolar septal tissue volume involving all cellular compartments of the septum compared with the control lung; as a result, alveolar-capillary surface areas and DL estimated by morphometry were restored to normal. In both groups, estimates of DL by the morphometric method agreed closely with estimates obtained by the physiological method during peak exercise. These data show that extensive lung resection in immature dogs stimulates a vigorous compensatory growth of alveolar tissue in excess of maturational lung growth, resulting in complete normalization of aerobic capacity and gas-exchange function at maturity. (+info)
Circulatory changes induced by isovolumic increase in red cell mass in fetal lambs.
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AIM: To verify whether extra uterine changes in total peripheral vascular resistance and cardiac output, caused by raised haematocrit, occur in fetal life and if they can be documented using conventional ultrasound techniques. METHODS: An exchange transfusion with packed red cells was performed on five fetal lambs at 140 days of gestation (weight 3.44, SD 0.48 kg); three others were used as controls. The haematocrit was raised from 44 +/- 3 to 64 (SD2)%. RESULTS: Body temperature, blood gas, and pH remained within normal limits. Blood viscosity increased from 5.3 (0.3) to 9.6 (1.6) cps. Combined cardiac output fell to 30% of its initial value. The pulsatility index (PI) remained unchanged in the umbilical artery (0.66, SD 0.1) and descending aorta (1.3, SD 0.3). A significant positive correlation was found between haematocrit and PI only in the carotid artery (r = 0.67, p < 0.01). CONCLUSION: In the fetus, as in adults, an increase in blood viscosity is associated with a fall in cardiac output. However, the low resistance and the relative inertia of the placental vascular bed blunt the velocimetric changes that could be induced in the lower body vascular system by an increase in resistance. Such changes were observed only in the carotid artery. These results could be of interest in the Doppler monitoring of human fetuses at risk of an abnormal increase in their haematocrit. (+info)
Urinary cGMP concentrations in severe primary pulmonary hypertension.
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BACKGROUND: Prognostic evaluation of patients with primary pulmonary hypertension (PPH) requires right heart catheterisation. The development of accurate non-invasive methods for monitoring these patients remains an important task. Cyclic guanosine monophosphate (cGMP) is an indicator of the action of natriuretic peptides and nitric oxide on target cells. Plasma and urinary cGMP concentrations are raised in patients with congestive heart failure in whom they correlate closely with haemodynamic parameters and disease severity. The aim of the present study was to determine whether the urinary concentration of cGMP could be used as a non-invasive marker of haemodynamic impairment in patients with severe PPH. METHODS: Urinary cGMP concentrations were measured in 19 consecutive patients with PPH, seven with acute asthma, and 30 normal healthy controls. RESULTS: Patients with PPH had higher urinary cGMP concentrations than asthmatic patients or normal healthy controls (p = 0.001). Urinary cGMP concentrations were higher in patients with severe haemodynamic impairment--that is, those with a cardiac index (CI) of < or = 2 l/min/m2 (p = 0.002)--and urinary cGMP concentrations were inversely correlated with CI (r = -0.69, p = 0.002) and venous oxygen saturation (r = -0.65, p = 0.003). CONCLUSION: Urinary cGMP concentrations may represent a non-invasive indicator of the haemodynamic status of patients with severe PPH. (+info)
Insulin action on heart and skeletal muscle glucose uptake in weight lifters and endurance athletes.
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There are no studies comparing myocardial metabolism between endurance- and resistance-trained athletes. We used 2-deoxy-2-[18F]fluoro-D-glucose and positron emission tomography combined with the euglycemic hyperinsulinemic clamp technique to compare the ability of insulin to stimulate myocardial, skeletal muscle, and whole body glucose uptake between weight lifters (n = 8), endurance athletes (n = 8), and sedentary men (n = 9). Maximal aerobic power (ml. kg- 1. min- 1) was higher in the endurance athletes (71 +/- 2, P < 0.001) than the weight lifters (42 +/- 2) and the sedentary men (42 +/- 2). Skeletal muscle glucose uptake (micromol. kg muscle- 1. min- 1) was enhanced in the endurance athletes (125 +/- 16, P < 0.01) but was similar in weight lifters (59 +/- 12) and sedentary (63 +/- 7) men. The rate of glucose uptake per unit mass of myocardium (micromol. kg- 1. min- 1) was similarly decreased in endurance athletes (544 +/- 50) and weight lifters (651 +/- 45) compared with sedentary men (1,041 +/- 78, P < 0.001 vs. endurance athletes and weight lifters). Both groups of athletes had increased left ventricular mass. Consequently, total left ventricular glucose uptake was comparable in all groups. These data demonstrate that aerobic but not resistance training is associated with enhanced insulin sensitivity in skeletal muscle. Despite this, cardiac changes are remarkably similar in weight lifters and endurance athletes and are characterized by an increase in left ventricular mass and diminished insulin-stimulated glucose uptake per heart mass. (+info)
Central and peripheral administration of endothelin-1 induces an increase in blood pressure in conscious trout.
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The central and peripheral cardiovascular effects of endothelin (ET)-1 and ET-3 were investigated in conscious rainbow trout. Both intracerebroventricular and intra-arterial injections of ET-1 (6. 25-25 pmol) but not ET-3 (25 pmol) caused a dose-dependent increase in mean dorsal aortic blood pressure and a concomitant decrease in heart rate. The hypertensive effects induced by intra-arterial and intracerebroventricular injection of ET-1 were associated with a significant (P < 0.05) increase in systemic vascular resistance. Intracerebroventricular injection of ET-1 induced a twofold higher pressor response than that caused by intra-arterial injection of ET-1 and provoked a barostatic gain that was reduced by 2.5- to 3-fold compared with that calculated after intra-arterial administration of the peptide. The ET receptor antagonist bosentan significantly (P < 0.05) attenuated these responses regardless of the route of administration. Finally, intra-arterial injection of ET-1 did not significantly modify plasma cortisol level. The present data demonstrate that intracerebroventricular and intra-arterial administration of very low doses of ET-1 produces hypertension in conscious trout. The lack of effect of ET-3 indicates that the hemodynamic actions of ET-1 are mediated both centrally and peripherally through ETA receptors. (+info)
Does gender influence the strength and mechanisms of the muscle metaboreflex during dynamic exercise in dogs?
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Ischemia of active skeletal muscle stimulates neuronal afferents within the muscle, which elicits a reflex increase in sympathetic nerve activity, systemic arterial pressure (SAP), and heart rate (HR), termed the muscle metaboreflex. We retrospectively investigated whether gender influences the activation of the muscle metaboreflex and the primary mechanisms used by this reflex, augmentation of cardiac output (CO) and peripheral vasoconstriction, using 15 female and 13 male chronically instrumented dogs exercising on a treadmill (3.2 km/h, 0% grade). Metaboreflex activation was achieved via progressive partial vascular occlusion of the terminal aorta during exercise. In both females and males, hindlimb ischemia elicited similar substantial increases in SAP (56.1 +/- 3.0 and 55.1 +/- 4.2 mmHg, respectively), HR (25.8 +/- 4.8 and 33.9 +/- 2.8 beats/min, respectively), and CO (1.39 +/- 0.3 and 1.64 +/- 0.2 liters, respectively) and a similar substantial decrease in renal vascular conductance (RVC; 42.7 +/- 4.9 and 42.9 +/- 5.3%, respectively). Both groups also demonstrated similar metaboreflex thresholds and sensitivities of SAP, HR, CO, and RVC. We conclude that the strength and mechanisms mediating the metaboreflex responses during dynamic exercise in dogs are not affected by gender. (+info)