Gibbe H. Parsons

Intracranial pressure during epileptic seizures.

A comatose 31-year-old male with presumed viral encephalitis and frequent partial motor seizures was paralyzed with pancuronium in an attempt to reduce recurrent elevation of intracranial pressure (ICP) associated with each seizure. ICP was continuously monitored with a Richmond Bolt and 5 electrographic seizures originating in the left frontal area were recorded. Each ictal episode was associated with stable blood pressure and an increase of ICP. The average seizure duration was 78 +/- 17 sec (mean +/- S.D.) and the average maximum increase of ICP above baseline during the seizures was 6.5 +/- 0.6 mm Hg with average peak ICP of 16.0 +/- 0.86 mm Hg. A simple mathematical model predicts the rate of increase of ICP, the peak ICP, the phase difference between maximum spike frequency and maximum ICP, and the rate at which ICP returns to pre-ictal values after termination of the seizure. The predicted values of ICP closely approximate the experimentally derived data. Therefore, the time course of the ICP appears to be determined by the frequency of the fundamental units of abnormal synchronized activity (the epileptogenic spike) and the CSF pressure-volume dynamics existing at the time of the seizure. An average increment of ICP per spike can be calculated for each seizure. The model also predicts that patients may develop high ICPs due to prolonged seizures. Prolonged unrecognized seizures may occur in patients who are therapeutically paralyzed as demonstrated by the case described here.

Acute ozone exposure increases bronchial blood flow in conscious sheep.

This study was initiated to determine the effects of ozone (O3) on sheep airway blood flow. Twenty-three nasally intubated sheep were exposed to filtered air (n = 5), 1 ppm O3 (n = 4), 2 ppm O3 (n = 5), 3 ppm O3 (n = 5), and 4 ppm O3 (n = 4) for 3 h. Bronchial artery flow (Qbr) was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored during the period of the exposures. Exposure to 3 and 4 ppm O3 resulted in a significant increase in Qbr (103 and 204% change, respectively) without affecting any of the other cardiopulmonary parameters measured. These results indicate that O3 induces a dose dependent increase in Qbr which is the result of a vasodilation of the bronchial vasculature which is not dependent upon changes in blood gases or upstream driving pressure.

AUTONOMIC CONTROL OF BRONCHIAL CIRCULATION IN AWAKE SHEEP DURING REST AND BEHAVIOUR

1. We tested the hypothesis that the pattern and the intensity of autonomic mechanisms causing vasoconstriction in the resting bronchial circulation of awake dogs also exists in awake sheep. It was also postulated that sighing behaviour and the associated bron‐chovascular dilatation induced by non‐adrenergic, non‐cholinergic (NANC) mechanisms observed in the dog exist in sheep.

Heart–Lung Interactions: The Sigh And Autonomic Control In The Bronchial And Coronary Circulations

1. The Darwin hypothesis that human and animal expressions of emotion are the product of evolution and are tied to patterns of autonomic activity specified to progress the emotion remains under challenge.

The value of serial serum angiotensin converting enzyme determinations in hospitalized patients with lung disease.

Abnormal serum angiotensin converting enzyme (ACE) activity has been reported in various human lung disorders and in laboratory animals with acute lung injuries. To test the value of serum ACE activity as an indicator of lung damage and its assistance in diagnosis or prognosis, 328 serum samples were obtained from 108 hospitalized patients with lung disease and 26 normal subjects. When patients were clinically grouped by disease entity, only the sarcoidosis group showed elevated mean serum ACE. Significantly increased serum ACE was found in 17 patients with various lung diseases (15% of hospitalized patients) 12 of whom also had concomitant liver disease. It is hypothesized that the liver may play a role in the normal metabolism of ACE being released by lung endothelial injury. Significantly low levels were seen in many acute and chronic lung injuries; specifically the groups with chronic obstructive lung disease, lung cancer, acute pneumonia, aspiration pneumonitis, gram-negative sepsis, acute myocardial infarction, and congestive heart failure. Serial measures of ACE in 71 patients with lung injuries showed that significantly decreasing levels over successive days were associated with a very high mortality. A single ACE measurement did not predict the presence or extent of lung injury, or aid in diagnosis or prognosis, but serial levels are of value prognostically. [Am J Med Sci 1984; 288(5):200–207.]

Neural control of the bronchial circulation

A distinction may be drawn between studies that define potential mechanisms of control, those that define components of control systems, and those that determine the priority of controls in the integrated system. It is the priority controls that determine survival in the environment. These different kinds of studies are necessary and complementary. In the case of the bronchial circulation, we continue with an era of defining potential mechanisms and component systems. These have been excellently reviewed by Godden (1990) and by Coleridge & Coleridge (1994). However, we have a long way to go before we establish priority neural controls in the integrated system. Cogent examples in the bronchial circulation might be the interaction at rest between neural controls and tonic NO released from vascular endothelium in determining basal autonomic tone. Another might be the autonomic controllers of bronchial resistance vessels reflexly evoked at the onset of exercise, and how these controls are modified by central temperature regulation as exercise continues. These kinds of data are necessary to understand evolutionary mechanisms that protect the organism from untoward environmental influence, and that point to support therapies for systems breakdown.

John Ludbrook APPS Symposium Coronary–Bronchial Blood Flow And Airway Dimensions In Exercise‐Induced Syndromes

1. We have an incomplete understanding of integrative cardiopulmonary control during exercise and particularly during the postexercise period, when symptoms and signs of myocardial ischaemia and exercise‐induced asthma not present during exercise may appear.

Effect of sodium metabisulphite on bronchial blood flow in conscious sheep : pharmacological modulation

1 Sodium metabisulphite (MBS) can induce bronchoconstriction in patients with asthma. We investigated the effects of MBS aerosol on bronchial blood velocity (Vbr) and pulmonary resistance in intubated conscious sheep. 2 Bronchial blood velocity was measured by implanting a 20 MHz ultrasonic Doppler flow probe on the common bronchial branch of the bronchoesophageal artery. 3 Inhaled MBS induced a dose‐dependent, transient increase in Vbr lasting for a few minutes without any changes in aortic and pulmonary artery pressures. There was some tachyphylaxis of the Vbr response to successive inhalations of MBS. 4 The cholinoceptor antagonist, ipratropium bromide and the H1 and H2 histamine antagonists, chlorpheniramine and cimetidine, had no significant effect on MBS‐induced increase on Vbr. The loop diuretic, frusemide, and the anti‐inflammatory drug, nedocromil sodium, which both inhibit MBS‐induced bronchoconstriction in patients with asthma, were also without effect. 5 We conclude that MBS induces bronchial vasodilatation in conscious sheep, and that this effect is not dependent on the release of histamine or other mediators, or an activation of cholinergic pathways.

Measurement of bronchial blood flow in the sheep by video dilution technique.

Bronchial blood flow was determined in five adult anaesthetised sheep by the video dilution technique. This is a new fluoroscopic technique for measuring blood flow that requires only arterial catheterisation. Catheters were placed into the broncho-oesophageal artery and ascending aorta from the femoral arteries for contrast injections and subsequent videotape recording. The technique yields bronchial blood flow as a percentage of cardiac output. The average bronchial artery blood flow was 0.6% (SD 0.20%) of cardiac output. In one sheep histamine (90 micrograms) injected directly into the bronchial artery increased bronchial blood flow by a factor of 6 and histamine (90 micrograms) plus methacholine (4.5 micrograms) augmented flow by a factor of 7.5 while leaving cardiac output unchanged. This study confirms the high degree of reactivity of the bronchial circulation and demonstrates the feasibility of using the video dilution technique to investigate the determinants of total bronchial artery blood flow in a stable animal model avoiding thoracotomy.

Differential effects of inhaled methacholine on circumferential wall and vascular smooth muscle of third-generation airways in awake sheep

Evolution and natural selection ensure that specific mechanisms exist for selective airway absorption of inhaled atmospheric molecules. Indeed, nebulized cholinoceptor agonists used in asthma-challenge tests may or may not enter the systemic circulation. We examined the hypothesis that inhaled cholinoceptor agonists have selective access. Six sheep were instrumented under general anesthesia (propofol 5 mg/kg iv, 2-3% isoflurane-oxygen), each with pulsed-Doppler blood flow transducers mounted on the single bronchial artery and sonomicrometer probes mounted on the intrapulmonary third-generation lingula lobe bronchus. Continuous measurements were made of bronchial blood flow (Q(br)), Q(br) conductance (C(br)), bronchial hemicircumference (CIRC(br)), and bronchial wall thickness (WALL TH(br)) in recovered, standing, awake sheep. Methacholine (MCh; 0.125-2.0 μg/kg iv), at the highest dose, caused a 233% rise in Q(br) (P < 0.05) and a 286% rise in C(br) (P < 0.05). CIRC(br) fell to 90% (P < 0.05); WALL TH(br) did not change. In contrast, nebulized MCh (1-32 mg/ml), inhaled through a mask at the highest dose, caused a rise in ventilation and a rise in Q(br) proportional to aortic pressure without change in C(br). CIRC(br) fell to 91% (P < 0.01), and WALL TH(br) did not change. Thus inhaled MCh has access to cholinoceptors of bronchial circumferential smooth muscle to cause airway lumen narrowing but effectively not to those of the systemic bronchovascular circulation. It is speculated that the mechanism is selective neuroparacrine inhibition of muscarinic acetylcholine receptors (M3 bronchovascular cholinoceptors) by prostanoids released by intense MCh activation of epithelial and mucosal cells lining the airway.