Biomedical Engineering Reference
In-Depth Information
Ischemia/Reperfusion
Reperfusion of ischemic myocardium has been reported to cause rapid degeneration
of endothelial function, characterized by a decreased release of NO in response to
endothelium-dependent vasodilators. A previous study showed that NO donors
given during reperfusion preserve coronary artery ring vasorelaxation and reduce
myocardial injury associated with ischemia and reperfusion. A study by Engelman
et al.
(1995) evaluated whether the NO precursor, L-Arg, could reduce ischemia/
reperfusion injury by preventing leukocyte-endothelial interactions. h ey induced
regional ischemia in an open-chest pig heart for 30 min followed by 90 min of
reperfusion. A preischemic 10-min intravenous infusion of 4 mg/kg/min of Arg
was compared to control pigs. h e results showed that L-Arg administration
reduced plasma levels of ICAM-1, E-selectin, and VCAM-1. Myocardial stunning
and arrhythmias were also reduced. A study by Hayashida
et al.
(2000) investigated
the ef ect of Arg on myocardial reperfusion injury. Isolated hearts were perfused
with blood at 37°C from a support rat. At er 20 min of aerobic perfusion, the
hearts were arrested for 60 min with warm blood cardioplegia given at 20 min
intervals. h is was followed by 60 min of reperfusion. h e hearts were divided
into three groups according to the supplemental drugs added to the cardioplegic
solution. h e control group received warm-blood cardioplegia. h e Arg group
received warm blood supplemented with Arg, and the third group received warm
blood supplemented with Arg and NG-nitro-L-arginine methyl ester (L-NAME,
an iNOS inhibitor). h e results showed that compared to the other two groups,
the Arg group showed early recovery of lactate metabolism and greater coronary
blood l ow during reperfusion. Levels of myocardial release of circulating ICAM-1
and E-selectin were lower in the Arg group.
Diabetes
Cardiovascular complications represent 80% of the causes of death in patients
with type 2 diabetes. Reactive oxygen and NO have recently been considered to
be involved in the cardiovascular complications of patients with type 2 diabetes.
A recent double-blind study tested the ef ects of L-Arg and N-acetylcysteine
administration in type 2 diabetic patients. Arg was used to enhance NO production,
and N-acetylcysteine was administered to ameliorate the antioxidant defense and
increase intracellular nitrosothiol concentrations, thus increasing NO availability.
Twenty-four male patients with type 2 diabetes and hypertension were randomly
divided into two groups of 12 patients and received either oral supplementation of
a placebo or N-acetylcysteine plus Arg for 6 mon. h ey found that N-acetylcysteine
plus Arg treatment caused reductions in blood pressure, high sensitivity C-reactive
protein, ICAM, VCAM, i brinogen, and plasminogen activator inhibitor 1. h ese
results suggest that N-acetylcysteine plus Arg administration improves endothelial
