David Royston

Retrograde tracing shows that CGRP-immunoreactive nerves of rat trachea and lung originate from vagal and dorsal root ganglia

The origins of sensory innervation of the lower respiratory tract are thought to be principally the nodose and jugular ganglia of the vagus nerve. It has been suggested and partially demonstrated that there is also a component arising from dorsal root ganglia, but the segmental levels involved are not known precisely. We have therefore investigated the origins of sensory nerves within the rat respiratory tract, particularly those containing calcitonin gene-related peptide (CGRP), using the technique of retrograde axonal tracing combined with immunohistochemistry. Injections of True blue were made into extra-thoracic trachea (n = 4 rats) and percutaneously into the right and left lung (n = 4 each). Retrogradely labelled neuronal perikarya were detected in vagal and dorsal root ganglia, and sympathetic chain ganglia. CGRP-immunoreactive cells were seen only in vagal and dorsal root ganglia. Tracheal innervation arose bilaterally in the vagal sensory ganglia but those on the right side represented the principal source; the majority of CGRP-containing neurons occurred in the jugular ganglion. A very small component of labelling occurred in spinal ganglia at levels C2-C6. The sensory innervation of the lungs was seen to arise predominantly from the ipsilateral dorsal root ganglia (45% of cells CGRP-immunoreactive) at levels T1-T6. In contrast to the trachea, the contribution of vagal sensory neurones to the lungs appeared to be less than that of the spinal ganglia. These results show that the sensory innervation of the rat lungs has a major origin in the dorsal root ganglia, in which almost half of the involved neurons contain CGRP, and confirm that most CGRP-immunoreactive nerves in the trachea arise in the right jugular ganglion.

HISTAMINE INCREASES LUNG PERMEABILITY BY AN H2-RECEPTOR MECHANISM

The effect of specific H1 and H2 receptor antagonists on bronchial reactivity and increase in lung epithelial permeability in response to inhaled histamine was measured in 5 non-smoking men (age range 24-36 years). Inhaled histamine produced a short-lived but consistent increase in permeability to 99Tc-diethylenetriamine penta-acetate. An H1-receptor antagonist, terfenadine (60 mg), protected against the bronchoconstrictor effect but had no significant influence on the increase in permeability. The H2-receptor antagonist ranitidine (150 mg) significantly reduced the permeability response without having an effect on bronchial reactivity. These results demonstrate that the bronchoconstrictor effect of histamine is mediated by H1 receptors and permeability increase is mediated by H2 receptors. H2-receptor mediated increase in lung epithelial permeability may be important clinically.

Adult respiratory distress syndrome after allogeneic bone-marrow transplantation: evidence for a neutrophil-independent mechanism

5 patients in whom the adult respiratory distress syndrome (ARDS) developed after bone-marrow transplantation (BMT) for chronic myeloid leukaemia are described. Donors in all cases were siblings who were matched for all major-histocompatibility-complex determinants. All patients were neutropenic to varying degrees at the onset of respiratory symptoms. Histological evaluation in all patients at necropsy showed diffuse alveolar damage with no evidence of intrapulmonary neutrophil sequestration. No patient had detectable levels of plasma peroxidation products, which were measured as an index of neutrophil oxidant function. Significantly increased clearance of inhaled 99mTc-diethylene-triamine-pentacetate was a uniform finding, suggesting impaired alveolar-capillary barrier function in keeping with ARDS. An increase in an index of lung epithelial permeability leading to ARDS may develop in neutropenic patients who have evidence of neither intrapulmonary neutrophil sequestration not tissue oxidant injury. ARDS after BMT is probably multifactorial in aetiology, but neutrophil-derived oxidant products play no part in its genesis.

Microprocessor-controlled hemodynamics: a step towards improved efficiency and safety.

Manual titration of sodium nitroprusside (SNP) is widely used for treatment of hypertension following cardiac surgery. This study compared conventional manual control with control by a research prototype of an automatic infusion module based on a proportional plus integral plus derivative (PID) negative feedback loop. Two groups of coronary artery bypass patients requiring SNP for postoperative hypertension were studied prospectively. In the first group, hypertension was controlled by manual adjustment of the SNP infusion rate, and in the second, the infusion rate was controlled automatically. The actual and desired mean arterial pressures (MAP) over consecutive ten-second epochs were recorded during the period of infusion. The MAP was maintained within 10% of the desired MAP 45.8% of the time in the manual group, compared with 90.0% in the automatic group, and the mean percent error in the automatic group was significantly less than in the manual group (P less than 0.01). It is concluded that adoption of such systems will result in improved patient safety and may facilitate more effective distribution of nursing staff within intensive care units.

Prevention of body temperature reduction (afterdrop) following hypothermic perfusion

This study investigated the possibility of preventing the postoperative reduction in body temperature (afterdrop) which followed a period of hypothermic cardiopulmonary bypass. In addition to warming all the infused fluids and inspired gases, the patients also had active warming by way of a system of hot water mattresses and limb jackets. In the eight male patients randomly allocated to the active treatment there were no significant changes on the central (aural) temperature in the five hours following the end of perfusion. The eight male control patients showed significant (p<0.05) falls in central temperature from 36.5 (0.3)°C at the end of bypass to 35.3 (0.2)°C and 35.0 (0.2)°C at one and two hours postperfusion. In addition, the mean skin temperatures were always significantly higher in the active warming group during the study period. This maintenance of a stable body temperature was reflected in the carbon dioxide production, which showed no significant changes in the actively warmed group. In the control group the carbon dioxide production was reduced from the preoperative value of 189 (26)ml/min (mean (SEM)) to 155 (9.2)ml/min (p<0.05) at two hours postperfusion. These data show that afterdrop following perfusion can be prevented by an aggressive rewarming policy and suggest that this may have beneficial effects in producing a metabolically and physiologically more stable patient.

The non‐steroidal anti‐inflammatory agent, indoprofen, does not protect against hydrochloric acid induced lung injury in the rat

The effects of pulmonary instillation of hydrochloric acid on solute flux from the lung (measured as the clearance of 99mTcDTPA) together with an index of oedema formation (the ratio of lung wet weight to lung dry weight) was measured in rats. There was a significant increase in 99mTcDTPA clearance (P <0.001) and also in lung wet:dry weight ratio (P<0.01) 4—5 h following acid challenge. There was no difference in the effects of challenge with acid of pH1 and pH2. In addition, intravenous injection of indoprofen (20mg/ kg) a non‐steroidal anti‐inflammatory agent failed to produce any beneficial effect on the variables under study when given after acid (pH2) challenge. There was also histological evidence of an influx and sequestration of granulocytes into the lung. Despite this, the plasma concentration of thiobarbituric acid reactive material (used as an index of cell‐derived, oxidant‐free radical production) was significantly reduced in all acid‐treated groups. These data show that hydrochloric acid will initiate a severe inflammatory response In the lung of the rat and that the non‐steroidal anti‐inflammatory agent indoprofen when given after the injury produced no evidence of a beneficial effect on this inflammatory response.

Prostacyclin, Cardiopulmonary Bypass and the Alveolar Capillary Membrane

Their reported lack of effect of bypass on the clearance of 99mTcDTPA appears to be due to the fact that the control values were abnormally rapid. Indeed the mean post bypass clearance of 35 minutes is not different from the previously reported figure of 29 minutes.’ What is differcnt is that the control values for normal lung were different from those of previous studies. For example, the same group quote ,a value for normal lung of 59(25) minutes (mean (SD)).’ How d o they explain their mean starting values of 35-40 minutes in this present study? On a separate issue, the authors have confirmed data from previous studies to show that there is white cell trapping in the lungs during the period of partial bypass. There is convincing evidence for prostacyclin’s ability to prevent white cell-endothelial interaction in vitro. However, is there any evidence to suggest that the infusion regime they administered produced tissue concentrations even close to that required to prevent aggregation iri citro. I t may be that analogues of prostacyclin may be produced which have much less cardiovascular effects and could thereby be administered in a dose which may prove beneficial, preventing microemboli and leukocyte margination in the pulmonary circulation. The apparently negative findings in this study may not have been due to the lack of efficacy of prostacyclin or prostacyclin derivatives. It remains to be determined if antiplatelet drugs play a part in cytoprotection from the deleterious effects ofcardioPulmonary bypass. David Roysrort MB ChB FFARCS, Senior Lecbypass. tiirer/Honorary Comtilrant, Royal Postgradrare Medical Scliool, Hantntersntirh Hoxpirnl, Drr Cam Rood, London IV12 OHS, UK.