Effect Of Alinidine Research Articles

ALINIDINE PREVENTS HYPOPERFUSION‐INDUCED TRANSMURAL FLOW REDISTRIBUTION IN ISOLATED PACED RAT HEARTS

1. The effect of alinidine on transmural flow redistribution during hypoperfusion was studied in the isolated rat heart. 2. Low flow perfusion of paced (5 Hz) rat Langendorff preparations with Tyrode's solution for 60 min resulted in loss of left ventricular pressure amplitude and contracture. 3. In the presence of 45.6 mumol/L alinidine in the hypoperfusion medium contractility was maintained and contracture was missing. 4. Myocardial sphere densities were assessed by infusion of fluorescent microspheres after 60 min of hypoperfusion. Histomorphometric evaluation of the left ventricular wall indicated marked redistribution of myocardial flow to the epicardium. Endo/epicardial quotients of sphere densities were significantly greater in alinidine-treated hearts. 5. Perfusion of hearts with 45.6 mumol/L alinidine for 30 min at a pressure of 80 cmH2O decreased coronary flow and contractility, but did not change the transmural quotient of sphere densities. 6. These results show that in isolated rat hearts with a ventricular wall of only 3-4 mm thickness severe hypoperfusion induces a shift in transmural flow distribution which is prevented by alinidine.

Effect of the ‘Specific Bradycardic Agent’ Alinidine on the Function of Ischemic Myocardium

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)

The effect of Alinidine on sinus node function and sinoatrial conduction time studied by atrial epicardial maps and EPS

The effect of Alinidine on sinus node function and sinoatrial conduction time studied by atrial epicardial maps and EPS

Interactions between alinidine and responses to acetylcholine, dopamine and 5-hydroxytryptamine of specific Helix central neurones.

Intracellular recordings were made from identified neurones in the brain of the snail, Helix aspersa. The effect of alinidine on the excitatory and inhibitory responses to acetylcholine and dopamine and on the excitatory response to 5-hydroxytryptamine (5-HT) was investigated. Alinidine was found to reduce the responses to acetylcholine and 5-HT and the excitatory response to dopamine but had no effect on the dopamine inhibitory response. pA2 values were determined for alinidine antagonism to indicate relative potency. The pA2 values against the excitatory responses of acetylcholine, dopamine and 5-HT were 5.8, 5.6 and 5.5 respectively. The pA2 value against acetylcholine inhibition was 3.5. From these studies it is suggested that alinidine interacts preferentially with the sodium inonophore, to a lesser degree with the chloride ionophore and not at all with the potassium ionophore on Helix central neurones.