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Myocardial ischemia-reperfusion injury and systemic inflammatory response in high-risk cardiac surgery

A clinical study of the effects of high-dose glucose-insulin treatment and the use of leukocyte-depleting filter

Juha Koskenkari

Lääketieteellinen tiedekunta, Lääketieteellinen tiedekunta, Oulun yliopisto

Lääketieteellinen tiedekunta, Anestesiologian klinikka, Oulun yliopisto

Lääketieteellinen tiedekunta, Kirurgia, Oulun yliopisto

Oulun yliopistollinen sairaala

Kansanterveyslaitos

Academic dissertation to be presented, with the assent of the Faculty of Medicine of the University of Oulu, for public defence in Auditorium 1 of Oulu University Hospital, on October 13th, 2006, at 12 noon

Oulun yliopisto

Esitarkastajat

Dosentti Tuula Kurki

Dosentti Markku Salmenperä

OULUN YLIOPISTO, OULU 2006

ISBN 951-42-8209-4 (PDF)

ISSN 1796-2234 (Online)

URN:ISBN:9514282094

Abstract

Cardiac surgery with cardiopulmonary bypass induces the activation of systemic inflammatory response syndrome (SIRS) and results in at least some degree of global myocardial ischemia. Although these responses are usually short-lived, they may lead to serious complications and organ system failures.

The present study evaluated the effects of high-dose glucose-insulin (1IU/kg/h) treatment (GIK) administered with the hyperinsulinemic normoglycemic clamp technique and a leukocyte-depleting filter on markers of systemic inflammatory response and myocardial ischemia-reperfusion injury in certain cardiac surgical risk groups.

The study involved four prospective randomized controlled clinical trials and 119 patients. Cardioprotective effects were measured as myocardial enzyme release, recovery of contractile function and incidence of arrhythmias in all studies. The hemodynamic and metabolic effects of high-dose glucose-insulin treatment were evaluated in patients admitted for combined aortic valve (AS) and coronary surgery (40) and for urgent coronary surgery (39), and the latter study also involved proinflammatory cytokine and C-reactive protein analyses. The impacts of leukocyte filter on the expression of neutrophil adhesion molecules along with proinflammatory cytokines were evaluated in patients admitted for combined aortic valve (AS) and coronary surgery (20) and for solitary coronary surgery (20).

The high-dose glucose-insulin treatment was associated with better preserved myocardial contractile function and less need for inotropic support after combined aortic valve and coronary surgery (I) and attenuation of postoperative CRP release after urgent coronary surgery (II). No effects on postoperative myocardial enzyme release (I, II) or on proinflammatory cytokine responses (II) were detected. The number of hypoglycemic events was low. The use of a leukocyte filter throughout the cardiopulmonary bypass period increased the neutrophil adhesion molecule CD11b expression in patients with both normal and prolonged CPB times and was associated with an enhanced proinflammatory cytokine response (III, IV).

In conclusion, high-dose glucose-insulin treatment is safe, but requires strict control of blood glucose level. It reduces the need for inotropic support in patients with compromised cardiac status. The use of leukocyte filter leads to increased leukocyte activation and proinflammatory reaction.

Asiasanat: cardiopulmonary bypass, glucose, insulin, leukocyte reduction procedures, myocardial reperfusion injury, systemic inflammatory response, thoracic surgery

Julkaistu painettuna:

serieslogo

Acta Universitatis Ouluensis

Medica

D 892

ISBN 951-42-8208-6

ISSN 0355-3221

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