In twelve healthy volunteers given nitroglycerin sublingually (1.6 mg) or epicutaneously (12 mg), venous distensibility was found to be maximal, even at low plasma concentrations (less than 0.2 ng/ml); there was no further change with increasing concentrations. Peripheral arterial resistance, on the other hand, decreased progressively with rising plasma concentrations and no distinct plateau was demonstrable, even at the highest plasma concentration measured (greater than 2.0 ng/ml).

The effects of nitroglycerin, infused intravenously at 3.4 and 7.5 micrograms/min over 30 min, on haemodynamic parameters were determined in the morning and the afternoon in a randomized, placebo-controlled study in 5 healthy volunteers. The mean steady-state concentrations of nitroglycerin reached in the plasma during the infusions of 3.4 and 7.5 micrograms/min were 0.35 +/- 0.06 ng/ml and 0.64 +/- 0.22 ng/ml, respectively. Wide inter-individual variation was noted. The nitroglycerin-induced increase in the orthostatic rise in heart rate and the change in digital-pulse-wave morphology roughly paralleled the plasma concentration, whereas the reduction in systolic blood pressure in the upright position was still evident 15 mins after the infusion, i.e. when nitroglycerin was no longer measurable in plasma. No significant diurnal variation in vascular sensitivity to the vasodilative action of nitroglycerin was demonstrable. The change in pulse-wave morphology resulting from the reduction in peripheral resistance (shift of the dicrotic wave in the descending limb towards the base-line) proved to be the most sensitive haemodynamic parameter.

A method is described of producing pulmonary embolism in the dog by the use of various-sized autologous clots made radiopaque. This method of experimental pulmonary embolism results in dilatation of the large- to small-sized pulmonary arteries and a consistent hemodynamic response in the pulmonary circulation, characterized by a marked rise in pulmonary arteriolar resistance with increased pulmonary arterial pressure but persistently normal pulmonary venous and "capillary" pressures. Data are presented to support the concept that the pulmonary hemodynamic changes that result from an initial pulmonary thromboembolism are primarily the result of vasoconstriction of the small pulmonary arteries or arterioles, presumably by a reflex mechanism. Mechanical blockage of the pulmonary vascular bed is considered to be of importance in causing hemodynamic alterations only after massive or repeated pulmonary embolism. The increase in pulmonary arteriolar resistance that results from the vasomotor response to pulmonary embolism is transient, whereas that due to mechanical blockage results in sustained pulmonary hypertension. Systemic arterial pressure does not show a consistent response to pulmonary embolism and could not be related to the hemodynamic alterations that occurred in the pulmonary circulation. Severe systemic hypotension resulted unpredictably but was more frequent after repeated or extensive pulmonary embolism. The systemic hypotensive reaction to pulmonary embolism is only in part due to a decreased cardiac output. The more severe responses are best explained on the basis of a vasomotor reflex producing a decrease in systemic arterial resistance. The two mechanisms of death in this experimental series were severe systemic hypotension with development of fatal ventricular arrhythmias and, almost as frequent, pulmonary edema that was characterized by severe pulmonary hypertension in the presence of a normal pulmonary venous pressure. There are many similarities between the experimental findings of this study and the clinical event of human pulmonary thromboembolism. Attention is drawn to the need for further investigation of the mechanism of the systemic arterial pressure response that often causes death and appears to be independent of the magnitude of the pulmonary hemodynamic changes.

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