Total and regional coronary blood flow were measured in dogs by left atrial injection of carbonized microspheres labeled with different radioactive isotopes (mean diameter 14 to 6lfi). Simultaneously blood was collected at 20 ml/min from a catheter tied into a peripheral artery. The ratios of flow to radioactivity in myocardium and arterial blood should be equal if microspheres are well mixed in the aortic root and are distributed regionally in proportion to flow. This was proved in seven right heart by-pass experiments where coronary venous drainage was measured directly. Also, less than 0.1% of total myocardial radioactivity appeared in coronary venous blood, even with hypoxemia and small microspheres.Total coronary flow in seven conscious dogs averaged 95 to 150 ml/min/100 g heart; and flow to the left ventricle was 111 to 169 ml/100 g. Although not validated independently, there was evidence that values for flow to each ventricle, the atria and the septum were correct.The radioactivity per gram of left ventricular subendocardial muscle was 2.5 times that of subepicardial muscle using microspheres 51 to 61yx in diameter, but the ratios were 1.4 and 1.3 using microspheres of mean diameters 20 to 23/i, and 14/i, respectively. It is unlikely that any of these microspheres measure blood flow to small portions of the ventricle. ADDITIONAL KEY WORDS left ventricular muscle flow coronary venous drainageright heart by-pass arteriovenous shunts right ventricular muscle flow arterioluminal shunts particle streaming• Coronary blood flow to the whole heart or to specific portions of it is difficult to measure

No abstract

We studied the differential response to inhaled salbutamol and ipratropium of 29 asthmatic patients, 18 intrinsic, 11 extrinsic, using peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Thirty minutes after a theoretically maximally bronchodilating dose of salbutamol (400 ,g) or ipratropium (80 ug), second doses frequently caused further bronchodilatation. We suspect that second doses may reach bronchi untouched by the first inhalation. Analysis of variance showed a powerful intrinsic versus extrinsic effect, and there were clearly differences between patients in their response to treatment (patient versus drug interaction) but these differences were not removed by dividing the patients into intrinsic and extrinsic groups. Results for the group as a whole favoured salbutamol, but examination of individual results by a pattern-recognition technique showed ipratropium equally effective in eight patients and more effective in three. All patients with a definite predominant salbutamol response were less than 40 years old. The response to salbutamol declined significantly with age, whereas that to ipratropium did not. In general in patients aged less than 40 years salbutamol is the drug of choice. With advancing age, and the apparent decline of fl-adrenergic responsiveness, the initially comparatively small response to ipratropium becomes relatively more important and may predominate. In older patients ipratropium, or continued therapy with both drugs, may be preferable.

Coughing was induced in seven normal and eight asthmatic subjects by giving successive inhalations of citric acid aerosols of progressively higher concentration (range 0.5-32%). A baseline cough response was obtained on each of four experimental days, and there was no significant difference between days in this respect. Then the subjects received by inhalation either a bronchodilator (salbutamol 5 mg or ipratropium 1 mg) or placebo, in a paired double blind crossover design. A second citric acid run followed and was used for paired drug-placebo comparisons. In the asthmatic subjects the cough response was diminished by both bronchodilators (p < 0.05), and the cough threshold was significantly higher after ipratropium but not salbutamol. In normal subjects no significant effects were found. Airways calibre was assessed, by an oscillatory technique that measures the resistance of the respiratory system (Siemens Siregnost FD 5), in four of the seven normal and all eight asthmatic subjects. The mean respiratory resistance was higher in asthmatic than in normal subjects, and fell significantly after both bronchodilators. In normal subjects smaller decreases in respiratory resistance occurred, significant only with salbutamol. The simplest hypothesis which explains the results relates change in cough response to altered neuroreceptor sensitivity associated with rapid changes in bronchial calibre.Cough is frequently the only presenting symptom in patients with bronchial asthma.' 2 The cough reflex arises from rapidly adapting receptors located in the larynx, trachea, and major bronchi.3'4 Impulses travel in afferent fibres in the vagus nerve to the cough centre in the brainstem. The tracheobronchial cough receptors are stimulated by touch and inhaled irritants5 and sensitised by bronchoconstriction, and this could explain why bronchoconstriction is associated with cough. Cough, in patients with uncomplicated bronchial asthma, is relieved by conventional aerosol bronchodilators.2 We have investigated cough induced by inhalation of citric acid in a group of normal and asthmatic subjects, and have assessed the effect of a f2 stimulant (salbutamol) and an anticholinergic (ipratropium) on the cough response. Methods SUBJECTSEight normal and eight asthmatic subjects were selected. All were non-smokers and had not had a

In 7 conscious dogs, left ventricular diastolic volume (V) was estimated by taking biplane cineradiographs with the left ventricular cavity previously outlined by permanent radiopaque markers. Left ventricular pressure (P) was measured with an implanted miniature transducer. There were two rapid filling periods during early and late diastole; little filling occurred during the middle third of diastole (diastasis). The diastolic pressure-volume relationship was approximately exponential and was fitted by the equation P = -a + be cY , where a, b, and c are positive constants; the relationship appeared to be determined principally by the elastic properties. The effects of infusions of saline, isoproterenol, calcium gluconate, and methoxamine suggested that viscous and inertial properties are also important determinants of diastolic left ventricular mechanics. No significant series viscosity was observed. Plastic properties were not detected. The elastic properties were not affected by agents having a positive inotropic effect. End-diastolic pressure often differed from that predicted by the exponential equation above, suggesting that it is not a reliable index of enddiastolic volume and left ventricular compliance. ADDITIONAL KEY WORDStantalum markers biplane cineradiography end-diastolic pressure left ventricular compliance isoproterenol elastic components myocardial plasticity series viscous element inertial properties left ventricular distensibility calcium methoxamine• The present study was undertaken to answer the following questions in the conscious dogs: (a) how does the volume of the left ventricle change during diastole; (b) what is the relationship between left ventric-