The effects of amrinone versus dobutamine on myocardial mechanics and energetics after hypothermic global ischemia

Ko, Wilson; Zelano, John A.; Fahey, A. Leilani; Berman, Karen F.; Lang, D; Isom, O. Wayne; Krieger, Karl H.

doi:10.1016/s0022-5223(19)33773-0

Cited by 15 publications

(4 citation statements)

References 25 publications

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“…Published reports in which isolate heart models were used, however, have relied on severe warm ischemic injury and crystalloid perfusates and have Individual experiments involved the use of two adult mongrel dogs as previously described. 16 In each experiment, the heart of one animal was used as the ex vivo isolated heart preparation that was cross-perfused by the second dog as the support animal. The animals were allowed food and water ad libitum the night before the experiments to avoid acute alteration of thyroid hormone levels.…”

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confidence: 99%

Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia

Klemperer¹,

Zelano²,

Helm³

et al. 1995

The Journal of Thoracic and Cardiovascular Surgery

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Cardiopulmonary bypass results in a "euthyroid sick" state. Recently, interest has focused on the relationship between low serum triiodothyronine levels and postoperative cardiovascular hemodynamics. The present study was undertaken to more clearly define the acute effects of triiodothyronine on myocardial mechanics and energetics after hypothermic global ischemia using an ex-vivo canine heart preparation to model the clinical condition. Experiments were performed on isolated hearts subjected to hyperkalemic arrest with 90 minutes of hypothermic (10 degrees C) ischemia. Isolated hearts were cross-perfused by euthyroid support dogs in which triiodothyronine levels spontaneously decreased by 65% to 75% (p < 0.01) after the initiation of cross-perfusion. In nine heart preparations, triiodothyronine (Triostat) was given as a bolus dose (0.2 micrograms/kg) after 1 hour of baseline data collection with a subsequent measurable rise in serum triiodothyronine levels (p < 0.01). In six postischemic hearts, reverse triiodothyronine was given as a 0.2 micrograms/kg bolus. Triiodothyronine was also administered to a group of eight nonischemic, continuously perfused isolated hearts. Intrinsic myocardial contractility was assessed by analysis of the preload recruitable stroke work area, energetic efficiency from the myocardial oxygen consumption-pressure-volume area relationship, and coronary vascular resistance from analysis of coronary flow and perfusion pressure. Acute administration of triiodothyronine to postischemic hearts improved the preload recruitable stroke work area from 9.5 +/- 1.42 to 14.9 +/- 2.03 x 10(7) erg/ml, a 56% increase from baseline (p < 0.001), but had no effect on the preload recruitable stroke work area of the nonischemic hearts. The inotropic response resulting from triiodothyronine treatment did not alter the myocardial oxygen consumption-pressure-volume area relationship. Triiodothyronine treatment was associated with significantly decreased coronary resistance and increased coronary flow through a range of diastolic loading conditions in the postischemic hearts. The biologically inactive thyroid hormone metabolite reverse triiodothyronine was without effect on any of the measured parameters. On the basis of these results, we conclude that the low triiodothyronine state of cardiopulmonary bypass can be reproduced in this isolated heart model and that acute triiodothyronine treatment results in a unique inotropic action manifest only in the postischemic reperfused myocardium and is accomplished without oxygen wasting effects.

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confidence: 99%

Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia

Klemperer¹,

Zelano²,

Helm³

et al. 1995

The Journal of Thoracic and Cardiovascular Surgery

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“…Also, as suggested with amrinone, administration of milrinone may offer some protection from post-bypass ischaemia, which would result in long term improved performance. 6 In summary, we have shown that in patients with mild depression of systolic function before operation, administration of a loading dose of milrinone 50 g kg 91 was associated with sustained haemodynamic improvement, in addition to increases in cardiac function that persisted until the end of surgery. Table 1 Haemodynamic data in the milrinone and placebo groups (mean (SEM)).…”

Section: Commentmentioning

confidence: 74%

A single dose of milrinone facilitates separation from cardiopulmonary bypass in patients with pre-existing left ventricular dysfunction

Lobato

Florete

Bingham

1998

British Journal of Anaesthesia

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Milrinone is used during cardiac surgery to facilitate separation from cardiopulmonary bypass (CPB) and/or to treat myocardial dysfunction in the post-bypass period. We have demonstrated, in patients with preoperative depression of systolic function undergoing aorto-coronary artery bypass surgery, sustained improvement in cardiac function after a single loading dose of milrinone 50 micrograms kg-1, administered at the end of bypass, thus significantly decreasing the need for beta-agonist therapy.

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“…Reversibly injured, stunned myocardium retains significant inotropic reserve (2) and is highly responsive to β‐adrenergic inotropes (3, 4). However, β‐adrenergic stimulation exacts a cost: catecholamines produce disproportionate increases in myocardial oxygen requirements relative to increases in mechanical function, thereby lowering myocardial O 2 utilization efficiency (5, 6), and depleting myocardial energy reserves (6–8). Thus β‐adrenergic stimulation jeopardizes stunned or failing myocardium by increasing its energy demand at a time when its energy reserves are low.…”

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confidence: 99%

Pyruvate: Metabolic Protector of Cardiac Performance

Mallet

2000

Proc Soc Exp Biol Med

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Abstract. Pyruvate, a metabolic product of glycolysis and an oxidizable fuel in myocardium, increases cardiac mechanical performance and energy reserves, especially when supplied at supraphysiological concentrations. The inotropic effects of pyruvate are most impressive in hearts that have been reversibly injured (stunned) by ischemia/reperfusion stress. Glucose appears to be an essential co‐substrate for pyruvate's salutary effects in stunned hearts, but other fuels including lactate, acetate, fatty acids, and ketone bodies produce little or no improvement in postischemic function over glucose alone. In contrast to pharmacological inotropism by catecholamines, metabolic inotropism by pyruvate increases cardiac energy reserves and bolsters the endogenous glutathione antioxidant system. Pyruvate enhancement of cardiac function may result from one or more of the following mechanisms: increased cytosolic ATP phosphorylation potential and Gibbs free energy of ATP hydrolysis, enhanced sarcoplasmic reticular calcium ion uptake and release, decreased cytosolic inorganic phosphate concentration, oxyradical scavenging via direct neutralization of peroxides and/or enhancement of the intracellular glutathione/NADPH antioxidant system, and/or closure of mitochondrial permeability transition pores. This review aims to summarize evidence for each of these mechanisms and to consider the potential utility of pyruvate as a therapeutic intervention for clinical management of cardiac insufficiency.

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The effects of amrinone versus dobutamine on myocardial mechanics and energetics after hypothermic global ischemia

Cited by 15 publications

References 25 publications

Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia

Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia

A single dose of milrinone facilitates separation from cardiopulmonary bypass in patients with pre-existing left ventricular dysfunction

Pyruvate: Metabolic Protector of Cardiac Performance

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