David Cottee

IS RENAL DOSE DOPAMINE PROTECTIVE OR THERAPEUTIC? NO

This article argues that dopamine infused in low doses has not been shown to avert the onset of or ameliorate the course of acute renal failure in critically ill patients. The inotropic and diuretic effects of dopamine are discussed, and its adverse effects are described. An attempt is made to offer an evidence-based role for low-dose dopamine, namely as a diuretic in ventilated, euvolemic patients, resistant to conventional diuretic therapy.

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.

Recent Views On Integrated Coronary Control: Significance Of Non‐Uniform Regional Control Of Coronary Flow Conductance

1. Previous work from this laboratory and others has shown that powerful autonomic influences modulate coronary flow. In particular, the parasympathetic nervous system produces vasodilatation when activated by baroreceptors via the vagus nerve.

BAROREFLEX CONTROL OF CORONARY BLOOD FLOW VARIES REGIONALLY IN AWAKE DOGS

1. Baroreflex responses to changes in aortic pressure were measured simulataneously in three main coronary regions of awake dogs.

Analysis of bronchovascular downstream blood pressure changes in exercising sheep.

The relative roles of neural and pressure gradient factors, causing a fall or maintenance of bronchial blood flow in exercising sheep, are unknown. These were examined in sheep prepared under thiopentone/isoflurane general anaesthesia with a pulsed Doppler probe mounted on the bronchial artery, and aortic pressure (Pa) catheter in superficial cervical artery. After recovery, Swan-Ganz catheters were inserted under local anaesthesia into the pulmonary artery. Bronchial flow and conductance (Qbr, Cbr), and pressure gradients (Pg; i.e. aortic minus right atrial, Pg_RAP; pulmonary artery, Pg_Ppa; and, left atrial (wedge) Pg_LAP) were derived from continuous records, after switching between downstream sites during and after moderately severe treadmill exercise (3.8 km.h−1, for 1.7 min, 6 min recovery). The protocol was repeated after combined α1,α2–adrenoceptor/cholinoceptor blockade using phentolamine methanesulfonate and methscopolamine bromide. Bronchial flow fell in both receptor intact (INT) and (BL) blocked state. Pa rose in INT, but downstream pressures rose only 3.7 (RAP), 2.8 (Ppa) and 2.0 (LAP) mmHg (P for each <0.05) in both INT and BL. Pg_RAP and Pg_Ppa did not rise, but Pg_LAP rose 4.0 mmHg (P < 0.05). In BL, Pa fell, as did Pg_RAP (7.0 mmHg, P < 0.05), Pg_Ppa (8.9 mmHg, P < 0.001), but Pg_LAP did not change. Thus, downstream pressures change by small amounts, and pressure gradients to RAP and Ppa sites do not change during moderately severe exercise in normal sheep. The fall in Qbr in INT is due to neural factors, but in BL is due to a fall in Pg. The relative rise in Pg_LAP in both INT and BL favours redistribution within total Qbr to the pulmonary capillary/vein/left atrium site.

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.