Improvement in Myocardial Function and Coronary Blood Flow in Ischemic Myocardium after Mannitol

Abstract

A B S T R A C T The purpose of this study was to evaluate the effect of hyperosmolality on the performance of, and the collateral blood flow to, ischemic myocardium. The myocardial response to mannitol, a hyperosmolar agent which remains extracellular, was evaluated in anesthetized dogs. Mannitol was infused into the aortic roots of 31 isovolumic hearts and of 15 dogs on right heart bypass, before and during ischemia. Myocardial ischemia was produced by temporary ligation of either the proximal or mid-left anterior descending coronary artery.Mannitol significantly improved the depressed ventricular function curves which occurred with left anterior descending coronary artery occlusion. Mannitol also significantly lessened the S-T segment elevation (epicardial electrocardiogram) occurring during myocardial ischemia in the isovolumic hearts and this reduction was associated with significant increases in total coronary blood flow (P < 0.005) and with increased collateral coronary blood flow to the ischemia area (P < 0.005).Thus, increases in serum osmolality produced by mannitol result in the following beneficial changes during myocardial ischemia: (a) improved myocardial function, (b) reduced S-T segment elevation, (c) increased total coronary blood flow, and (d) increased collateral coronary blood flow.

The effect of mannitol following permanent coronary occlusion.

“…In the present study, mannitol did not increase myocardial blood flows in either the normal or ischemic areas 30 minutes after institution of the treatment, in contrast to reports by Willerson, Hutton et al9' [14][15][16]22 The reason for this discrepancy is not entirely clear but several points should be noted. First, serum osmolarity had risen only 13 mOsm/L on the average in the present experiment at the time when myocardial blood flows were measured, compared to increases of mOsm/L in previous experiments.9 [14][15][16]22 Moreover, the regulation of coronary blood flow in isolated perfused hearts22 and in anesthetized dogs on right heart bypass9 14 may differ from the physiologically more normal preparation used in the present studies.…”

“…First, serum osmolarity had risen only 13 mOsm/L on the average in the present experiment at the time when myocardial blood flows were measured, compared to increases of mOsm/L in previous experiments.9 [14][15][16]22 Moreover, the regulation of coronary blood flow in isolated perfused hearts22 and in anesthetized dogs on right heart bypass9 14 may differ from the physiologically more normal preparation used in the present studies. In addition, the increases in myocardial blood flow observed in unanesthetized preparations following mannitol infusion were accompanied by marked increases in aortic pressure and cardiac output'5' 16 in contrast to the measurements reported here.…”

“…16 In addition, hyperosmolarity was found to improve myocardial performance both in isolated cardiac muscle '7 '" and in the intact heart with normal coronary perfusion and after regional ischemia. 22 These results led to the speculation that treatment with hypertonic mannitol might be of value in salvaging ischemic myocardium.23 However, quantitative effects of mannitol on infarct size have not been reported in a preparation with permanent coronary occlusion. Accordingly, the present study was undertaken to evaluate the effects of a four hour treatment with hypertonic mannitol on the extent of myocardial damage 24 hours after acute coronary occlusion in dogs.…”

Influence of Calcium on the Inotropic Actions of Hyperosmotic Agents, Norepinephrine, Paired Electrical Stimulation, and Treppe

“…Maximal inotropic effects occurred between 5 and 8.0 mM calcium and further elevation to 11.0 nmM was without additional influence. The effect of hyperosmotic sucrose and mannitol on papillary muscle performance was compared with that of 10' M norepinephrine at calcium concentrations of 2.5 and 10.0 mM and with paired electrical stimulation in 10.0 mM calcium. Both norepinephrine and the hyperosmotic agents produced significant increases in developed tension and in the maximal rate of tension rise (dT/dt) in Krebs-Ringer in 2.5 and 4.0 mM calcium.…”

“…Hyperosmotic agents have also been shown to improve ventricular function, reduce the extent of myocardial injury, and improve total and collateral coronary blood flow during acute coronary insufficiency in anesthetized animals (10) and to reduce hypoxic depression in isolated cat papillary muscle (11). When osmolality rises to over 100 mosmol above control levels (> 400 mosmol/kg HsO), both the contractile elements and the viscoelastic components of the myocardium are altered, but below that level hyperosmolality affects only the contractile elements of the heart (9, 12).…”