Systolic time intervals--a new technique in clinical pharmacology

Systolic time intervals (STI) are unique in describing cardio-vascular function in terms of time alone. Although the STI were first adequately described over 60 years ago, it is only recently that they have been applied in a scientific way to the study of drug action in man. The STI are highly sensitive to changes in myocardial contractility, left ventricular filling pressure, peripheral resistance, heart rate, and intra-cardiac electrical conduction and electro-mechanical coupling. Early investigators tended to regard STI as a specific measure of contractility, and they also used inappropriate methods for correcting the STI for changes in heart rate. The reputation of the method was not enhanced by the fact that many studies were performed in an open fashion and without placebo control. Furthermore, the STI have never been popular with clinicians because they many sometimes be normal in spite of the presence of obvious severe heart disease. Now, however, STI are being used increasingly in clinical pharmacological studies. They can be recorded quickly, easily and painlessly with inexpensive apparatus which is readily available; they carry no risk, and multiple recordings can be made without discomfort. The lack of specificity of the STI can be mitigated by combining them with measurements of heart rate, blood pressure, the high-speed surface electrocardiogram, and cardiac output. The most promising applications of the STI in clinical pharmacology are as a screening test for cardiovascular activity of new compounds, and in the examination of dose-response relationships and agonist-antagonist interactions.