Effects of morphine on ventricular function and myocardial contractile force

Js, Vasko; Henney, R. Peter; Rk, Brawley; Oldham, H. Newland; Ag, Morrow

doi:10.1152/ajplegacy.1966.210.2.329

Cited by 62 publications

(14 citation statements)

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“…Thus, it appears that morphine induces a complex reaction, the beta adrenergic effects slightly overshadowing any direct negative inotropic action of the drug. A previous study by Vasko, Henney, Brawley, Oldham, and Morrow, also found a positive inotropic effect with morphine and attributed it solely to release of adrenal catecholamines (9). While the latter may contribute to the positive inotropic response to morphine, it is not the sole mechanism, since morphine also increased contractility after adrenalectomy in the present study.…”

Section: Effects Of 025 Mg/kg Ms Every 15 Min In the Normal Consciousupporting

confidence: 78%

Effects of morphine on coronary and left ventricular dynamics in conscious dogs.

Vatner¹,

Marsh²,

Swain³

1975

J. Clin. Invest.

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A B S T R A C T We studied the effects of i.v. 2 mg/kg morphine sulfate (MS) on coronary blood flow and resistance, left ventricular (LV) diameter and pressure (P), rate of change of pressure (dP/dt), and dP/dt/P in conscious dogs. An initial transient reduction in coronary vascular resistance, associated with increases in heart rate, dP/dt, dP/dt/P, and reductions in LV enddiastolic and end-systolic size were observed. This was followed by a prolonged increase in mean coronary vascular resistance, lasting from 5 to 30 min, while heart rate, arterial pressure, and LV end-diastolic diameter returned to control levels and dP/dt/P remained slightly but significantly above control. At 10 min, late diastolic coronary flow had fallen from 44+3 ml/min to a minimum level of 25±3 ml/min, while late diastolic coronary resistance had risen from 1.68±0.10 to 3.04±0.28 mm Hg/ml/min. Morphine also induced substantial coronary vasoconstriction when heart rate was held constant. Neither the MS-induced coronary vasoconstriction nor the positive inotropic response was abolished by bilateral adrenalectomy. The positive inotropic response of MS was reversed after beta blockade, but not the coronary vasoconstriction. Alpha receptor blockade abolished the late coronary vasoconstrictor effects of morphine, and only dilatation occurred. In anesthetized dogs MS failed to produce late coronary vasoconstriction. Coronary vasoconstriction was not observed in conscious dogs after a respiratory-depressant dose of morphine, 10 mg/kg i.v. Smaller doses of MS, 0.25 mg/kg every 15 min, produced significant coronary vasoconstriction after a total dose of 0.75 mg/kg in the conscious dogs.

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Section: Effects Of 025 Mg/kg Ms Every 15 Min In the Normal Consciousupporting

confidence: 78%

Effects of morphine on coronary and left ventricular dynamics in conscious dogs.

Vatner¹,

Marsh²,

Swain³

1975

J. Clin. Invest.

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“…The negative inotropic and chronotropic actions of morphine and other opioids have been reported previously (11,12,29,33), and they are thought to be mediated by ␦-or -opioid receptors (3) or nonopioid receptors (33). Reports of positive inotropic action of morphine in intact animals are thought to be the result of sympathoadrenal discharge (30).…”

Section: [ 3 H]ne Uptake In Cardiac Synaptosomesmentioning

confidence: 92%

A highly potent peptide analgesic that protects against ischemia-reperfusion-induced myocardial stunning

Soong

Zhao

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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We recently discovered an opioid peptide analgesic, 2′,6′-dimethyltyrosine (Dmt)-d-Arg-Phe-Lys-NH2([Dmt1]DALDA), that can protect against ischemia-induced myocardial stunning. In buffer-perfused hearts, 30-min global ischemia followed by reperfusion resulted in a significant increase in norepinephrine (NE) overflow immediately upon reperfusion and significant decline in contractile force (45%). Pretreatment with [Dmt1]DALDA before ischemia completely abolished myocardial stunning and significantly reduced NE overflow (68%). In contrast, pretreatment with morphine before ischemia only provided brief protection against myocardial stunning and no reduction in NE overflow. [Dmt1]DALDA inhibited [3H]NE uptake into cardiac synaptosomes in vitro (IC50 = 3.9 μM), whereas morphine had no effect. Surprisingly, protection against myocardial stunning was apparent even when hearts were perfused with [Dmt1]DALDA only upon reperfusion, whereas reperfusion with morphine had no effect. Binding studies with [3H][Dmt1]DALDA revealed no high-affinity specific binding in cardiac membranes, suggesting that the cardioprotective actions of [Dmt1]DALDA are not mediated via opioid receptors. These findings suggest that [Dmt1]DALDA is a potent analgesic that may be useful for myocardial stunning resulting from cardiac interventions or myocardial ischemia.

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“…Morphine has been reported to decrease (6)(7)(8) or to increase (9,10) myocardial contractility. However, the specificity of some of the cardiovascular effects of peripherally injected morphine and enkephalins has been questioned, and their mediation by sympathetic nerve activation (9,10) and histamine release from mast cells (11) has been reported.…”

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confidence: 99%

Enkephalins have a direct positive inotropic effect on cultured cardiac myocytes.

Laurent¹,

Marsh²,

Smith³

1985

Proc. Natl. Acad. Sci. U.S.A.

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Enkephalins have peripheral vascular effects, and enkephalinergic innervation of the heart has been reported. To determine whether enkephalins have direct effects on myocardium, we studied the effects of [Leu5]Enkephalin has been reported to increase the norepinephrine-stimulated positive chronotropic response and 45Ca uptake in guinea pig (4). Furthermore, circulatory anatomy is such that enkephalins released from adrenal medulla flow directly through the vena cava to the right heart and pulmonary circulation where they could exert direct effects. Their short half-life, however, may limit the concentrations reaching brain centers that could affect cardiovascular responses (5).There is substantial evidence that opiates and opioid peptides have cardiovascular effects. Morphine has been reported to decrease (6)(7)(8) or to increase (9, 10) myocardial contractility. However, the specificity of some of the cardiovascular effects of peripherally injected morphine and enkephalins has been questioned, and their mediation by sympathetic nerve activation (9, 10) and histamine release from mast cells (11) has been reported.Whether or not circulating or prejunctionally released opioid peptides exert a direct postjunctional effect on the cardiac myocyte is unknown. The existence of direct effects of opioid peptides on the heart cannot be concluded from studies with preparations containing intact nerve endings and catecholamine stores. Thus, a detailed analysis of the direct cardiac effects of enkephalins may best be undertaken in a preparation devoid of intact neural elements. We report here the effects of enkephalins and enkephalin-like peptides Leu- MATERIALS AND METHODSTissue Culture. Primary monolayer cultures of beating chicken embryo ventricular cells were prepared as described (12). Briefly, fragments of embryonic chicken ventricules 10 days in ovo were dissociated by repeated cycles oftrypsinization. The resulting cell suspension (4 x 105 cells per ml) was plated in 100-mm culture dishes. The medium consisted of a bicarbonate-buffered physiological salt solution containing 40% medium 199 (GIBCO), 6% fetal calf serum, and 54% balanced salt solution containing glucose. Final concentrations in the culture medium were 144 mM Na, 4.0 mM K, 0.97 mM Ca, 18 mM HCO3, 0.8 mM Mg, and 131 mM Cl. Cultures were incubated in humidified 5% C02/95% air at 37°C. Spontaneously and synchronously contracting confluent monolayers were present by 3 days in culture, at which time experiments were performed. For contractility and ion-flux experiments, cells were grown on 25-mm circular glass coverslips.Contractility Measurements. Changes in the position of a cell or attached microsphere border in a monolayer were assessed by the use of an optical-video system as described (12). Briefly, a glass coverslip with attached cells was continuously superfused in a chamber provided with inlet and exit ports. The chamber was placed on the stage of an inverted phase-contrast microscope (Leitz Diavert). The cells were magnified with a x40 ob...

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Effects of morphine on ventricular function and myocardial contractile force

Cited by 62 publications

References 0 publications

Effects of morphine on coronary and left ventricular dynamics in conscious dogs.

Effects of morphine on coronary and left ventricular dynamics in conscious dogs.

A highly potent peptide analgesic that protects against ischemia-reperfusion-induced myocardial stunning

Enkephalins have a direct positive inotropic effect on cultured cardiac myocytes.

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