Normalization of the blunted ventilatory response to acute hypoxia in congenital cyanotic heart disease.

Patients with congenital cyanotic heart disease have a blunted ventilatory response to hypoxia, but the permanence of the blunting is disputed. To determine how early the blunted ventilatory response develops and whether it is reversible, we studied three groups of children and young adults: five (seven to 13 years of age) with acyanotic heart disease, eight (seven to 16) with cyanotic congenital heart disease (arterial oxygen saturation, 55 to 83 per cent), and 13 (seven to 17) whose cardiac defects were repaired (arterial oxygen saturation, 93 to 98 per cent). The ventilatory response to acute hypoxia was subnormal in the hypoxemic children in that their ventilation showed little increase when arterial oxygen saturation fell by 10 to 20 per cent, compared to a 150 to 300 per cent increase in the control subjects. This characteristic even appeared in a seven-year-old patient, indicating that the disorder occurs in early life. The appearance of blunted ventilatory response is delayed when hypoxia from birth is less severe. After operation, with return of the arterial hypoxemia to normal, the response was in the normal range. We conclude that the blunted response is reversible.

Cholinergic mechanisms on the heart and coronary circulation.

1. The effects of rapid intracoronary injection of acetylcholine (ACh) were studied in anaesthetized open chest dogs. Changes in phasic coronary blood flow were followed with non-cannulating electromagnetic flow probes and in contractile force with isometric strain gauges.2. Increasing doses of ACh from 0.01 to 100 mug produced progressively larger increases in systolic and diastolic coronary blood flow and progressive decreases in end-diastolic vascular resistance which were blocked by atropine but not by propranolol.3. Contractile force showed both negative and positive responses. The negative inotropic effect was small and was blocked by atropine but not by propranolol. The threshold for the negative inotropic response was higher than for the coronary vasodilator effect and the dose response curve was flatter. The positive inotropic response usually showed two components. One component reached its maximum 13 to 18 s after injection, had a high threshold (over 1 mug), was potentiated by atropine and blocked by propranolol. The other reached its maximum 25 to 60 s after the injection, had a threshold between 0.01 and 0.1 mug, and was blocked by atropine but not by propranolol.4. These results suggest that the coronary dilator response, the negative inotropic response and part of the positive inotropic response are mediated through "muscarinic" receptors. The remaining component of the positive inotropic response appears to involve catecholamine release.