Effects of Ang 1-7, taurine and glutamine in the recovery of myocardial dysfunction after transient ischaemia
M Munteanu, V Cobet, I I Popovici, L Ciobanu, I Popovici, V Ivanov, M PopoviciAbstract
Background
Myocardial dysfunction induced by transient ischemia is reversible during reperfusion, a phenomenon referred to as reversible cardiomyopathy. The extent of recovery depends, in part, on the pre-ischemic functional state of the myocardium.
Aim
The in vitro evaluation of effects Ang 1-7, taurine and glutamine action before ischaemia on myocardium functional recovery during reperfusion.
Material and methods
Effects of Ang 1-7 (10-6 M), taurine (50 mM) or glutamine (20 mM) were studied using the model of isolated perfused rat heart by Langendorff and Neely-Roveto methods. Remedies have been infused in Krebs solution during 15 min before ischemia which was reproduced by reducing coronary flow till 30% of initial level with a duration of 15 min. Reperfusion lasted up to 100 min, a time needed for a total functional recovery, but functional indices have been assayed at 15 min of reperfusion, a period highly manifested by calcium and oxygen paradox of reperfusion. In control series no any medication. ANOWA/t-Student test was used and data were estimated as M±SD.
Results
All remedies demonstrated a similar effect regarding recovery of pump function at 15 min of reperfusion, contractility and diastolic relaxation. Such, aortic jet exceeded control level (9.2±2.6 ml/min) by 40.2-46.7%, and LV systolic pressure by 23.8-25.7% (control: 96.5±11.4 ml/min). Noteworthy, isovolumic contraction and relaxation significantly improved: increment of +dP/dTmax was up to 10.1% and -dP/dTmax increased up to 13.2%. In series where IP included natural remedies diastolic stiffness raise was lesser by 18.9-20.6% vs control (42.3±5.6 mmhg/ml). Remarkable, the inotropic response of the heart on norepinephrine action at 15 min of reperfusion was impaired, and increase of LV systolic pressure and cardiac output was double less versus preischemic pattern. Taurine increased especially LV systolic pressure by 16.9% vs control, and glutamine especially increased cardiac output by 19.8% due to higher tachycardia. Ang 1-7 showed best effect regarding coronary flow reserve during stimulation the heart by acetylcholine, compared to control: 19.8% vs 12.6% (in preischemic heart – 23.5%). Finally, full functional recovery of control heart was established at 70 min of reperfusion, in series with remedies – at 50 min.
Conclusion
Administration of angiotensin-(1–7), taurine, or glutamine prior to low-flow ischemia accelerates myocardial functional recovery and improves left ventricular performance during early reperfusion in isolated rat hearts, supporting their potential role as pharmacological preconditioning agents.