Binding of [3H]-5-hydroxytryptamine to human coronary artery and bypass graft vessels.

OBJECTIVES: 5-Hydroxytryptamine (5-HT) has a wide range of vascular effects mediated via specific receptors and it has been suggested to be a mediator in ischemic heart disease. The aim of the present study was to localise the 5-HT receptors within the vessel wall. METHODS: Epicardial coronary arteries obtained from patients undergoing cardiac transplantation, internal mammary arteries from heart donors and saphenous veins from patients undergoing coronary bypass surgery, were sectioned and incubated with [3H]-5-HT for in vitro receptor autoradiography. RESULTS: Microscopic analysis of high resolution autoradiographic images revealed a similar pattern of [3H]-5-HT binding in epicardial coronary and internal mammary artery, where it predominated in the lamina muscularis. In the saphenous vein, binding increased towards the adventitia which showed dense, displaceable binding to the vasa vasorum as well as to nerve-like structures, from which binding was only partially displaced. Computer-assisted densitometric analysis of low resolution autoradiographs revealed a high degree of specific binding to all vessels examined. CONCLUSIONS: The distribution of the [3H]-5-HT binding is different in the saphenous vein compared to epicardial coronary and internal mammary artery. The dense binding to vasa vasorum in the saphenous vein suggests a role for 5-HT in closure of these nutrient vessels, which could contribute to the formation of atherosclerotic changes in saphenous vein grafts.

Effects of NO inhalation on pulmonary leukocyte sequestration and blood volume in porcine endotoxaemia.

OBJECTIVE: Sequestration and migration of activated neutrophils plays a major role in the pulmonary injury typical of septic shock and the adult respiratory distress syndrome. Inhaled NO may counteract alveolar-capillary damage attributed to activated neutrophils. The present study describes a method to directly demonstrate the effects of NO inhalation on endotoxin-induced sequestration of 99mTc-labelled leukocytes [As(t)] in the lungs of pigs. DESIGN: Prospective controlled study. SETTING: Laboratory for experimental surgery at a university medical centre. SUBJECTS: Anaesthetised and ventilated pigs. INTERVENTIONS: To induce inflammatory shock 26 animals received a continuous endotoxin infusion. Thirteen animals inhaled NO from the start of the experiments, while 13 served as controls. In 13 animals from both groups, leukocytes were labelled in vitro and reinjected, while in the 13 others erythrocytes were labelled in vivo to provide corrections for changes in blood volume. MEASUREMENTS AND RESULTS: The pulmonary distribution of 99mTc-labelled leukocytes or erythrocytes was studied dynamically for 180 min. After correction for changes in pulmonary and heart blood volume (PBV, HBV), leukocyte sequestration curves were generated. Endotoxin induced pulmonary vasoconstriction, reduced PBV, impaired oxygenation, and caused a maximum increase in As(t) of 30% in the lungs. NO inhalation attenuated pulmonary vasoconstriction and the reduction in PBV. The maximum increase in As(t) was reduced to 15% of baseline. CONCLUSIONS: Inhaled NO exerts its main vascular effects in the pulmonary microvasculature, the primary site of physiological neutrophil margination and pathological adhesion of activated leukocytes. Early use of NO inhalation may offer protection against the development of more lasting pulmonary failure in septic shock by reducing leukocyte sequestration in the lungs.

Elastic pressure-volume curves of the respiratory system reveal a high tendency to lung collapse in young pigs.

OBJECTIVE: To study pressure-volume (P/V) curves over a wide pressure and volume range in pigs. DESIGN: Dynamic and static P/V curves (P(dyn)/V and P(st)/V) and compliance of the respiratory system were studied. The effects of recruitment, positive end-expiratory pressure (PEEP) and body position were analysed. SETTING: Research animal laboratory. MATERIALS: Seven anaesthetised, paralysed and ventilated healthy pigs of 21 kg. MEASUREMENTS: P/V curves up to a pressure of about 40 cmH(2)O were recorded with a computer-controlled ventilator. P(st)/V curves were obtained with the static occlusion method and P(dyn)/V curves during an insufflation at a low, constant flow rate. RESULTS: P(dyn)/V recording showed a complex pattern. During the insufflation compliance increased, fell, increased and fell again. A 2nd P(dyn)/V recording immediately following the 1st one was displaced towards higher volumes and showed only one maximum of compliance. The difference between the two curves reflected: (1) lung collapse during a period of 5 min of ventilation at zero end-expiratory pressure (ZEEP) following a recruitment manoeuvre, (2) recruitment during the measurement of the 1st P(dyn)/V curve. These observations were similar in the supine and in the left lateral position. After ventilation at PEEP, 4 cmH(2)O, the signs of collapse and recruitment were reduced. It was confirmed that PEEP offers a partial protection against collapse. P(st)/V curves showed higher volumes and higher compliance values compared to P(dyn)/V curves. This reflects the influence of viscoelastance on P(dyn)/V curves. CONCLUSION: The study demonstrates a particularly strong tendency to lung collapse in pigs.

Intestinal and hepatic perfusion and metabolism in hypodynamic endotoxic shock. Effects of nitric oxide synthase inhibition.

BACKGROUND: Inhibition of nitric oxide synthase (NOS) has been claimed to be beneficial in septic shock. We investigated the overall and regional effects of a NOS-inhibitor on perfusion and metabolism during severe endotoxic shock. METHODS: Nineteen anaesthetised pigs were catheterised and ultrasonic flow-probes were placed around the portal vein, the hepatic artery, and the superior mesenteric artery. Thirteen animals were given a 3-h infusion of endotoxin; in 6 of these an infusion of NG-nitro-L-arginine-methyl-ester (L-NAME) was started an hour after the start of endotoxin while 7 animals served as controls and received endotoxin only. Six animals were sham operated with no further intervention. RESULTS: Endotoxin produced a hypodynamic shock with pulmonary hypertension. L-NAME did not increase arterial blood pressure, but deepened the fall in cardiac output and enhanced the increase in systemic and pulmonary vascular resistance. The infusion of endotoxin caused a decrease in flows in all regions. The addition of L-NAME induced a further decrease in the mesenteric artery flow only. L-NAME had no additional effect on hepatic artery flow ratio, while a transient decrease was seen in mesenteric flow ratio. Portal flow ratio decreased in the control group only. Global as well as regional oxygen extraction increased in both groups, more so in the L-NAME group. Lactate levels increased with no differences between the groups. CONCLUSION: In hypodynamic endotoxic shock, L-NAME infusion enhanced pulmonary vasoconstriction and increased left ventricular afterload. The resulting hypoperfusion caused an increase in mortality. The effects of L-NAME on global and mesenteric blood flow and metabolism were similar, while L-NAME had no additional effects on hepatic hypoperfusion or oxygen extraction. Thus, nitric oxide does not seem to be a major factor in the preservation of hepatic perfusion during unresuscitated endotoxic shock.

Cerebral blood volume (CBV) in humans during normo- and hypocapnia: influence of nitrous oxide (N(2)O).

BACKGROUND: It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N(2)O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia. METHODS: Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40-50% N(2)O, and hypocapnia + 40-50% N(2)O. CBV was measured after (99m)Tc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning. RESULTS: Global CBV during normocapnia and inhalation of 50% O(2) was 4.25 +/- 0.57% of the brain volume (4.17 +/- 0.56 ml/100 g, mean +/- SD) with no change during inhalation of 40-50% N(2)O in O(2). Decreasing carbon dioxide (CO(2)) by 1.5 kPa (11 mmHg) without N(2)O inhalation and by 1.4 kPa (11 mmHg) with N(2)O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 +/- 0.10% of the brain volume per kilopascal (0.26 +/- 0.10 ml x 100 g(-1) x kPa(-1)) without N(2)O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml x 100 g(-1) x kPa(-1)) during N(2)O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in Delta CBV when CO(2) is changed. N(2)O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or Delta CBV/Delta CO(2) in these nine subjects. CONCLUSIONS: Nitrous oxide inhalation had no effect either on CBV or on the normal CBV-CO(2) response in humans.

The effects of nitric oxide inhalation on respiratory mechanics and gas exchange during endotoxaemia in the pig.

BACKGROUND: In the adult respiratory distress syndrome, nitric oxide (NO) inhalation improves oxygenation through reducing ventilation-perfusion mismatching, but detailed information on the pulmonary effects of NO inhalation in septic shock is scarce. The present study investigated the effects of inhaled NO on alveolar dead space (Vdalv) and venous admixture as well as on respiratory system compliance (Crs) and respiratory system resistance (Rrs) in a porcine model of septic shock. Protective effects of NO are discussed. METHODS: Thirteen anaesthetised and ventilated pigs were given an infusion of endotoxin for an observation time of 220 min to induce acute lung injury (ALI). In the NO-early group (n=6), an inhalation of 60 ppm NO was started simultaneously with the endotoxin infusion and continued for 190 min. In 7 control/NO-late animals, 60 ppm NO was administered for 30 min following 190 min of endotoxin infusion. Haemodynamics, single-breath CO2-, pressure-, and flow signals were recorded. RESULTS: Endotoxin induced haemoconcentration, pulmonary vasoconstriction, and a decrease in Crs, while venous admixture, Vdalv, and Rrs increased. In the NO-early group, the pulmonary vasoconstriction was attenuated, no increase in pulmonary venous admixture or in Vdalv was seen before cessation of NO, and the improvements in oxygenation outlasted the NO inhalation. In the control/NO-late group, the NO inhalation reversed the changes in dead space and venous admixture. NO had no effect on the changes in respiratory mechanics. CONCLUSION: In porcine ALI, 60 ppm NO diminishes pulmonary vasoconstriction and improves gas exchange by reducing pulmonary venous admixture and alveolar dead space, but does not prevent a fall in Crs. NO inhalation may help prevent long-lasting pulmonary failure.

Elastic properties of the lung and the chest wall in young and adult healthy pigs.

Understanding of the elastic pressure/volume (Pel/V) curve is still limited in health and disease. The aim of the present study was to elucidate the Pel/V curve and elastance of the respiratory system (ERS) lung (EL) and chest wall (ECW) in healthy pigs. Six young (20.8 kg) and seven adult (58.9 kg), anaesthetized, paralysed and ventilated pigs were studied. Pel/V curves were recorded at zero end-expiratory pressure (ZEEP) and at positive end-expiratory pressure (PEEP) up to 40 cmH2O with a computer controlled ventilator during an insufflation at a low, constant flow. Pel/V curves of the respiratory system showed a complex pattern in both young and adult pigs. During the insufflation, ERS decreased, increased, fell, and increased again. A second Pel/V curve recorded immediately after the first one showed lower elastance and only one early fall in ERS. ECW fell over the initial segment and was then nearly stable. Difference between 1st and 2nd curves reflected changes in EL caused by recruitment during the 1st insufflation. At PEEP, such signs of collapse and recruitment were reduced. A strong tendency to lung collapse contributes to a complex pattern of elastic pressure/volume curves. At low volumes and distending pressures the chest wall contributes significantly to changes in respiratory system elastance.