Ventricular vulnerability in diabetes and myocardial norepinephrine release.
Previously the authors have observed a reduction of the ventricular fibrillation threshold (VFT) in a mild diabetic model. This investigation examines the role of more severe hyperglycemia in altering the ventricular fibrillation threshold and how the sympathetic nervous system modulates the response. Alloxan diabetes was induced in eight male mongrel dogs 3-5 years of age (Group 2), for comparison with matched controls (Group 1). Hemoglobin A1c rose from 2.9 +/- .4-7.8 +/- .3% and body weight was maintained with daily insulin. After 1 year, anesthesia was induced with chloralose and an electrode catheter placed at the right ventricular apex. VFT was 41.7 +/- 1.8 ma in Group 1 and 27.8 +/- 2.1 ma in the diabetics of Group 2 (p less than .001). There was significantly greater decline of VFT in response to epinephrine infusion in Group 2. The threshold in diabetics rose to normal levels after infusion of the beta-blocking agent, esmolol. Subsequently, the response of the cardiac sympathetic system was assessed during ventricular pacing at 200 beats/minute. Serial paired blood samples were taken from catheters in the aorta and coronary sinus for catecholamine assay by HPLC. Both groups had similar coronary blood flow responses by the thermal method, as well as changes in arterial pressure. While no change occurred in Group 1, a progressive rise of norepinephrine (NE) concentration was observed in coronary venous effluent of Group 2 (p less than .01). The basal arterial-coronary sinus difference was-123 +/- 52 pg/ml, which rose during pacing in Group 2 to a peak of -376 +/- 9.3 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Fusilli
L
L
Department of Medicine, University of Medicine and Dentistry, New Jersey Medical School, Newark 07103-2757.
Lyons
M
M
Patel
B
B
Torres
R
R
Hernandez
F
F
Regan
T
T
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D002304:Cardiac Pacing, Artificial; D002851:Chromatography, High Pressure Liquid; D003326:Coronary Circulation; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D004285:Dogs; D004298:Dopamine / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006439:Hemodynamics; D008297:Male; D008929:Mitochondria, Heart / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000378:metabolism
D001786:Blood Glucose; D004298:Dopamine; D006442:Glycated Hemoglobin; D009638:Norepinephrine