Graphical analysis of drug effects in the dog heart-lung preparation--with particular reference to the pulmonary circulation and effects of norepinephrine and 5-hydroxytryptamine.

Abstract

Our new method for the graphical analysis of drug effects in the dog heart-lung preparation was extended to pulmonary circulation. The equilibrium points, at which the cardiac output (CO) curve and venous return (VR) curve cross each other in the right atrial pressure (RAP)-CO and left atrial pressure (LAP)-CO relations, were directly recorded on two X-Y recorders. The VR curves were obtained by inducing cardiac fibrillation and simultaneously occluding the pulmonary arterial trunk. The competence test, which was utilized previously for recording the CO curve in the RAP-CO relation (Ishikawa et al., 1978), was confirmed to be a good procedure for the CO curve in the LAP-CO relation. During the competence test, the mean pulmonary pressure (Pmp) which is the intercept of the pulmonary VR curve on the LAP axis in the LAP-CO relation was changed as much as the change in the systemic reservoir blood level, with little change in the slope of the pulmonary VR curve. When the reservoir blood level was 100 mm above the superior vena cava and the aortic pressure was 70 mmHg (control), the Pmp value was 136 +/- 7 mmH2O (n = 24). The slope of the pulmonary VR curve was not so different from that of the systemic VR curve in RAP-CO relation. Raising aortic pressure to 100 mmHg caused a shift of the equilibrium point to the right and slightly downwards, increased the Pmp value by 42.9 +/- 9.9 mmH2O (delta Pmp) and decreased the reservoir blood volume by 26.2 +/- 6.4 ml (delta V). The ratio delta V/delta Pmp was 0.66 +/- 0.11 ml/mmH2O. The continuous infusion of norepinephrine 4 micrograms/min caused a shift of the equilibrium point to the left and upwards, decreased the Pmp value by 67.1 +/- 19.1 mmH2O and increased the reservoir blood volume by 35.3 +/- 7.2 ml. The ratio delta V/delta Pmp was 0.56 +/- 0.16 ml/mmH2O. The continuous infusion of 5-hydroxytryptamine at the rate of 60 micrograms/min caused a shift of the equilibrium point almost vertically and downwards, increased Pmp value by 34.8 +/- 3.2 mmH2O and decreased the reservoir blood volume by 45.8 +/- 10.1 ml. The ratio delta V/delta Pmp was 0.88 +/- 0.10 ml/mmH2O.