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AR-L 115 in coronary artery disease: positive inotropic effects and increase of left-ventricular pump function
Insights
AR-L 115 significantly improved cardiac function in patients with coronary artery disease under stress. This drug enhanced pump function without causing myocardial ischemia, offering a potential therapeutic benefit.
Area of Science:
- Cardiology
- Pharmacology
- Cardiovascular Physiology
Background:
- Congestive cardiomyopathy treatment can be challenging.
- Advanced coronary artery disease (CAD) patients may experience detrimental effects from cardiac-enhancing drugs due to increased energy demands.
- Assessing the impact of novel agents on myocardial function under stress is crucial.
Purpose of the Study:
- To evaluate the hemodynamic and electrocardiographic (ECG) responses to AR-L 115 in patients with CAD and angina.
- To determine if AR-L 115 improves left ventricular (LV) pump function during stress without inducing myocardial ischemia.
Main Methods:
- Ten patients with CAD and pacing-induced angina or elevated LV-end diastolic pressure (LVEDP) were studied.
- Clinical, hemodynamic, and ECG parameters were monitored before and during peak AR-L 115 effect (2 mg/kg bolus).
- Pacing stress tests were repeated under AR-L 115 to assess myocardial ischemia and pump function.
Main Results:
- AR-L 115 administration eliminated ECG and hemodynamic evidence of myocardial ischemia during stress.
- Significant improvements were observed in cardiac index (+43%), heart rate (+16%), stroke index (+27%), ejection fraction (+20%), VCF (+31%), and dp/dt max (+39%).
- LVEDP normalized to resting levels, while LV-systolic pressure and end-diastolic volume remained unchanged (P > 0.05).
Conclusions:
- AR-L 115 effectively enhances LV pump function in CAD patients during stress conditions.
- The drug improves cardiac performance without inducing myocardial ischemia, suggesting a favorable risk-benefit profile for this population.
- AR-L 115 represents a promising therapeutic option for managing cardiac dysfunction in advanced CAD.
Abstract:
1. AR-L 115 improves pump function in patients with advanced and fully treated congestive cardiomyopathy. Since, in spite of such beneficial responses, the energy cost involved might be detrimental when used in advanced coronary artery disease, we monitored clinical haemodynamic and ECG responses to AR-L 115 (2 mg/kg body weight, bolus) in ten patients with coronary artery disease who had developed angina pectoris and/or pathological increases in left ventricular-end diastolic pressure (LVEDP) at the end of a 1 min pacing stress test. 2. When subjected to these stress conditions again (but this time during the peak effect of AR-L 115), there was no longer evidence of ischaemic myocardial impairment, neither clinically by ECG or haemodynamically. 3. There were (average) increase of 43% in cardiac index, 16% in heart rate, 27% in stroke index, 20% in ejection fraction, 31% in VCF and 39% in dp/dt max, while LVEDP decreased to normal values as if at resting conditions. All changes were significant (P less than 0.05). 4. LV-systolic pressure and end diastolic volume (P greater than 0.05) remained the same. Thus the AR-L 115-induced improved LV-pump function was accomplished under stress conditions in the absence of evidence for myocardial ischaemia.