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The negative inotropic and chronotropic effects of intravenous R 56865 during percutaneous transluminal coronary
A J Pijl1, H B Van Wezel, J J Koolen
1Department of Anaesthesiology, University of Amsterdam, The Netherlands.
Insights
R 56865 did not show anti-ischaemic effects in patients undergoing percutaneous transluminal coronary angioplasty. High doses of R 56865 caused significant hypotension and reduced cardiac contractility, indicating potential adverse effects.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Coronary artery disease (CAD) poses significant risks, necessitating effective anti-ischaemic therapies.
- Percutaneous transluminal coronary angioplasty (PTCA) is a common intervention for CAD.
- Evaluating novel pharmacological agents for anti-ischaemic activity is crucial.
Purpose of the Study:
- To assess the anti-ischaemic potential of R 56865 in patients with CAD undergoing PTCA.
- To investigate the haemodynamic effects of R 56865 at various intravenous dosages.
Main Methods:
- Haemodynamic profiling, including cardiac output and coronary sinus blood flow (CSBF), was performed at baseline.
- Left ventricular pressure and contractility parameters were measured before and after balloon inflations, with and without R 56865.
- R 56865 was administered intravenously at 20 mg, 30 mg, and 40 mg dosages.
Main Results:
- No significant differences in ST-segment changes or angina pectoris were observed between placebo and R 56865 (20 mg).
- Low to moderate doses (20 mg, 30 mg) of R 56865 did not alter haemodynamic parameters from baseline.
- The highest dose (40 mg) induced severe hypotension, decreased cardiac contractility, and reduced CSBF, with adverse patient responses.
Conclusions:
- R 56865 demonstrated no anti-ischaemic efficacy under the studied conditions.
- The highest dose of R 56865 was associated with significant adverse haemodynamic effects, including hypotension and reduced cardiac function.
Abstract:
The present study was designed to evaluate the potential anti-ischaemic activity of R 56865 in patients with coronary artery disease, scheduled to undergo percutaneous transluminal coronary angioplasty (PTCA). At baseline a complete haemodynamic profile, including cardiac output and coronary sinus blood flow (CSBF) was obtained. In addition, left ventricular pressure and contractility parameters were measured. These parameters were also measured before and after additional balloon inflations, preceded by placebo and R 56865 i.v. R 56865 was infused intravenously at three different dosages, namely: 20 mg (n = 8), 30 mg (n = 2), 40 mg (n = 2). No significant differences were observed between placebo and R 56865 (20 mg) concerning time to onset and duration of ST-segment changes and symptomatic angina pectoris, respectively. The other parameters did not show differences compared with the baseline values when R 56865 (20 and 30 mg) was infused. However, the two patients receiving a dose of 40 mg R 56865 developed a dramatic decrease in systolic and diastolic blood pressure, left ventricular (LV) systolic pressure, peak positive dP/dt and the CSBF (ranging from 30-50%), while the LV end-diastolic pressure increased by 100%. The two patients who received this dose became pale and cyanotic and did not respond to verbal commands. In summary, no anti-ischaemic effects of R 56865 were observed under these conditions, whereas at the highest dose (40 mg) R 56865 induced hypotension and a reduction in cardiac contractile force.
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