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Effect of the 'specific bradycardic agent' alinidine on the function of ischemic myocardium
1Department of Cardiac and Vascular Surgery, German Heart Center, Munich.
Insights
Alinidine (ALI) improves heart function in ischemic myocardium by reducing heart rate, unlike beta-blockers. This specific bradycardic agent enhances systolic shortening in ischemic heart segments without negatively impacting overall heart function.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Beta-blockers can impair myocardial function in coronary artery disease patients by reducing heart rate (HR).
- Specific bradycardic agents may offer a safer alternative for managing heart rate in these patients.
Purpose of the Study:
- To investigate the effects of alinidine (ALI) on ischemic myocardium in a canine model.
- To determine if ALI improves myocardial function in the presence of ischemia.
Main Methods:
- Anesthetized open-chest dogs underwent coronary artery constriction to induce ischemia.
- Measurements included left ventricular pressure, contractility, coronary blood flow, and myocardial segment dimensions.
- Alinidine was administered intravenously, and its effects were assessed at various doses and heart rates.
Main Results:
- Alinidine dose-dependently reduced heart rate and increased ventricular filling.
- Ischemic myocardial segment shortening significantly improved with ALI administration.
- Improvements in ischemic function were correlated with heart rate reduction, not changes in preload, afterload, or contractility.
Conclusions:
- Alinidine effectively improves systolic shortening in ischemic myocardium.
- The beneficial effects of ALI are primarily attributed to heart rate reduction, mitigating myocardial oxygen demand.
Abstract:
In patients with coronary artery disease, the reduction of heart rate (HR) by beta-blockers can further impair myocardial function by reducing the contractility and coronary perfusion. This is possibly not the case for "specific bradycardic agents" like alinidine (ALI). The effect of ALI on ischemic myocardium, therefore, was studied in anesthetized open-chest dogs measuring left ventricular end-diastolic pressure (LVedP), dP/dt, aortic pressure (AoP) by catheter tip manometers, coronary blood flow (Q) electromagnetically, end-diastolic length (edL) and systolic shortening (sdL in %edL) of ischemic (RISC) and non-ischemic (NISC) wall segments by sonomicrometry. Group A (n = 11): Left coronary artery constriction to reduce Q (-53%) and poststenotic sdL (-54%), then i.v. injection of ALI (0.25 + 0.25 + 0.5 + 1.0 mg/kg), thereafter atrial pacing at HR before ALI. Group B (n = 9): Installation of an aorto-coronary bypass, pump-perfused at 50% of free flow, infusion of ALI into the bypass. The results showed that ALI iv dose-dependently reduced HR from 135/min to 90/min, LVedP rose from 8.6 to 10.0 mmHg and NISC-edL from 14.1 to 14.6 mm indicating increased ventricular filling. Non-ischemic systolic shortening did not change. Ischemic systolic shortening was improved from 9.2% to 17.5%, which was not due to an increase in RISC-edL (14.8 versus 14.7 mm), enhanced RISC-Q (13 versus 12 ml/min), reduced AoP (86 versus 84 mmHg) or change in inotropy (dP/dtmax: 2290 versus 2240 mmhg/s), but the increase in RISC-sdl correlated closely (r greater than 0.85) to the reduction in HR (oxygen-demand).(ABSTRACT TRUNCATED AT 250 WORDS)