European Journal of Heart Failure 2005 7(7):1180-1182; doi:10.1016/j.ejheart.2005.02.001
© 2005 European Society of Cardiology
Attenuation of postoperative noradrenaline need by nitric oxide inhibition using L-NMMA
Anders Franco-Cerecedaa,*,
Peter Holma,
Fredrik Bredinb and
Christoffer Addinga
a Department of Cardiothoracic Surgery, Karolinska University Hospital S-171 76 Stockholm, Sweden
b Department of Cardiothoracic Anaesthesia, Karolinska University Hospital 171 76 Stockholm, Sweden
* Corresponding author. Tel.: +46 8 517 708 26; fax: +46 8 32 27 01. E-mail address: andfra{at}mbox.ki.se
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Abstract
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In the present report we describe that NG-monomethyl-L-arginine
acetate, a non-specific nitric oxide synthesis inhibitor, administered
at 1 mg kg
–1 h
–1 to a patient with critical hypotension
following mitral valve surgery combined with passive containment
surgery, increased the urinary output and arterial blood pressure
while the need for noradrenaline was rapidly attenuated. Again
increasing the noradrenaline infusion in the presence of NG-monomethyl-L-arginine
acetate caused a dramatic increase of the blood pressure.
Key Words: Congestive heart failure • L-NMMA • Mitral valve surgery • Nitric oxide • Passive containment surgery
Received November 1, 2004; Accepted February 8, 2005
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1. Background
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A 57 year old female with known idiopathic cardiomyopathy was
admitted for surgery. Cardiac catheterization had revealed predominant
left ventricular failure with a left ventricular (LV) ejection
fraction of 14% and LV end-diastolic diameter of 92 mm. There
was a marked mitral regurgitation (grade III/IV) secondary to
the ventricular dilatation. At referral she was in NYHA class
III in spite of maximal medical treatment including ACE-inhibition,
β-blockade and diuretics. Noteworthy her resting systolic
arterial blood pressure (SBP) was around 80 mm Hg.
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2. Methods
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After discussing surgical options with the patient, including
possible benefits with passive containment surgery using the
ACORN Cardiac Support Device (CSD)® in combination with
mitral valve surgery, ethical permission was obtained from the
Ethics Committee of the Karolinska Hospital and written consent
was obtained from the patient. The CSD is a mesh-like polyester
fabric with bidirectional compliance placed around the heart
in order to reduce wall stress and reshape the dilated heart
from a spherical to a more ellipsoidal shape.
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3. Results
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The patient underwent cardiopulmonary bypass (104 min), aortic
cross-clamp (45 min) and ante-and retrograde blood cardioplegia
with a core temperature of 34 °C.
The surgical procedure was primarily uneventful with implantation of a 26 mm Carpentier–Edwards anuloplasty ring combined with application of the CSD. Due to low blood pressure and low cardiac output with equalized pulmonary artery and systemic arterial pressures the patient was put on levosimendan, noradrenaline and adrenaline when going off pump. An intra-aortic balloon pump was inserted and the patient was transferred to the ICU with an SBP of 65–70 mm Hg.
In spite of increasing the noradrenaline dose (maximal dose 720 ng kg–1 min–1) there was a gradual decline in the patient's condition with decreased urinary output (
45 ml h–1) and continuously low SBP (65 mm Hg; without the intra aortic balloon pump augmentation; systemic vascular resistance around 1040 dyn s–1 cm2 –1) and a cardiac index of <2.5 l min–1 m2 –1 (Table 1). The decision was therefore taken to start infusion of NG-monomethyl-L-arginine acetate (L-NMMA) at as dose of 1 mg kg–1 h–1. Within 1 h the urinary output had increased to >100 ml h–1 and the SBP increased to 75–80 mm Hg without any major effects on cardiac index or pulmonary artery pressure. At the same time the noradrenaline dose could be reduced to 400 ng kg–1 min–1. Increasing the dose of noradrenaline during the L-NMMA infusion caused a dramatic effect on the SBP with an increase to >100 mm Hg (Fig. 1). The L-NMMA infusion was terminated after 5 h and following removal of the IABP, withdrawal of pharmacological inotropic support, the patient left the ICU on day seven and has now been discharged to home.
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4. Conclusion
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It is well known that blockade of nitric oxide (NO)-synthesis
produces vasoconstriction when administered to humans and non-selective
NO-blockade has earlier been shown to be effective in cardiogenic
shock as well as septic chock.
[1]. The importance of NO in
the setting of cardiac failure has also been evaluated
[2].
The mechanisms responsible for the presently observed beneficial
effect of
L-NMMA is unclear but there are several plausible
explanations. Low doses of NO are generally considered to improve
cardiac contractility while high doses have a negative inotropic
effect
[3]. Cardiac inducible nitric oxide synthesis is high
in patients with severe heart failure and in systemic cytokine
activation
[2]. High cardiac levels of NO attenuate the response
to adrenergic receptor stimulation. Furthermore, it has been
shown that NO levels are high following cardiac surgery
[4].
Therefore, NO-synthase inhibition may act centrally on the heart
and/or peripherally on the vascular bed to induce both positive
inotropic effects as well as increasing vascular resistance.
Interestingly, we only observed a small transient increase in
pulmonary artery pressure by
L-NMMA infusion in spite of previous
concerns of detrimental pulmonary hypertension
[5].
Although the present report only represents a single patient we believe that NO-synthase inhibition may prove beneficial in situations with severe hypotension unresponsive to other surgical or pharmacological interventions.
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Acknowledgement
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Supported by the J Elgqvist Foundation, the M Kleberg Foundation
and Goljes Foundation.
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References
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- Cotter G., Kaluski E., Blatt A., Milovanov O., Moshovitz Y., Zaidenstam R., et al. L-NMMA (a nitric oxide synthase inhibitor) is effective in the treatment of cardiogenic shock. Circulation (2000) 101:1358–1363.[Abstract/Free Full Text]
- Drexler H. Nitric oxide synthesases in the failing human heart. Circulation (1999) 99:2972–2975.[Free Full Text]
- Massion P.B., Feron O., Dessy C., Balligand J.L. Nitric oxide and cardiac function. Circ Res (2003) 93:388–405.[Abstract/Free Full Text]
- Mayers I., Hursts T., Puttagunta L., Radomski A., Mycyk T., Sawacki G., et al. Cardiac surgery increases the activity of matrix metalloproteinases and nitric oxide synthase in the human heart. J Thorac Cardiovac Surg (2001) 122:746–752.[Abstract/Free Full Text]
- Gachot B., Bedos J.P., Veber B., Wolff M., Regnier B. Short-term effects of methylene blue on hemodynamics and gas exchange in humans with septic chock. Int Care (1995) 21:1027–1031.[CrossRef]
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Abstract
1. Background
) is the stepwise reduction of Noradrenalione infusion from 720 to 400 (ng kg–1 min–1). Note the dramatic effect on blood pressure by increasing noradrenaline infusion to 720 (ng kg–1 min–1 
) after 1 h of L-NMMA infusion.