Changes in Endothelium-Derived Vascular Regulatory Factors During Dobutamine-Stress-Induced Silent Myocardial Ischemia in Patients With Kawasaki Disease

Abstract

The changes in endothelium-derived vascular regulatory factors during dobutamine (DOB)-induced myocardial ischemia (MI) were investigated in 21 patients with Kawasaki disease aged from 11 months to 18 years. They were classified into an ischemia group (8 patients) and a non-ischemia group (13 patients) based on the results of 99m Tc myocardial scintigraphy and DOB stress 99m Tc myocardial scintigraphy. In the ischemia group, MI was relatively mild, because there were ischemic changes on the electrocardiogram and no significant symptoms during DOB stress. Catheters were positioned near the orifice of the coronary artery (Ao) and at the coronary sinus (CS). Hemodynamics and the blood concentrations of lactic acid and endothelin-1, as well as NO3 -, 6-ketoprostaglandin F1 , and thromboxane B2, (which are inactive metabolites of nitric oxide, prostaglandin I2 and thromboxane A2, respectively), were measured at rest and after DOB stress (maximum dose: 30 g·kg -1 ·min -1 ). The CS/Ao ratio was determined for all parameters. The rate-pressure product, an index of work load, and the cardiac index were significantly increased by DOB stress in both groups. Coronary angiography showed no vasospasm of the epicardial coronary arteries before or after DOB stress in either group. The plasma concentrations of endothelin-1 and 6-keto-prostaglandin F1 were significantly increased after DOB stress in the ischemia group, but the serum concentration of NO did not increase. The lack of an increase in NO production during DOB stress may have contributed to the worsening of MI in patients with Kawasaki disease. (Jpn Circ J 1999; 63: 503 -508)

Evaluation by High-Resolution Ultrasonography of Endothelial Function in Brachial Artery After Kawasaki Disease and the Effects of Intravenous Administration of Vitamin C.

“…Ogawa et al demonstrated a high level of soluble endothelin-1 not only in the acute phase of KD but also in the recovery stage, 22 and it has also been demonstrated that the plasma concentration of endothelin-1 significantly increased after dobutamine stress after KD. 23 A recent study showed that endothelin-1 could induce an increase in superoxide anion production, 24 which rapidly reacts with and breaks down nitric oxide. Vitamin C is a potent watersoluble antioxidant and effective scavenger of free radicals, such as the superoxide anion.…”

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“…(r) ALA preserved P and S, especially P, in survivors and non-survivors. (r) ALA increases nitric oxide levels (protective against VT/VF, silent ischemia [65,66]), reduces nuclear kappa B, and is essential for certain mitochondrial oxidative enzymes. Decreased nitric oxide levels prolong QTc [67,68].…”

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“…(r)ALA restores and recycles vitamins A, C, E, and glutathione. 14,15 It improves hyperglycemia, endothelial dysfunction, endothelial nitric oxide levels (protective against VT/VF), silent ischemia, [16][17][18][19] and reduces nuclear kappa B-is essential for certain mitochondrial oxidative enzymes-and normal P and S.…”