Myocyte Contracture, Vascular Resistance, and Vascular Permeability After Global Ischemia in Isolated Hearts From Alloxan-Induced Diabetic Rabbits

Abstract

Coronary vascular hemodynamics, albumin permeation, and myocyte contractility were assessed in isolated hearts from 6-mo alloxan-induced diabetic (ALX-D) rabbits during 3 h of reperfusion after 40 min of global no-flow ischemia. Residue-detection data, generated during the single passage of a bolus of 125 l-labeled bovine serum albumin ( 125 I-BSA) through the coronary vasculature, were used to estimate indices of vascular function, including the mean transit time of 12S I-BSA, the fractional rate of intravascular clearance of 12S I-BSA, and 125 I-BSA permeation of coronary vessels. During reflow after ischemia in hearts from control rabbits, vascular resistance increased approximately three times that at baseline, left ventricular end-diastolic pressure (LVEDP) increased 8-10 times, and maximum +dP/df recovered 0.4 times baseline, whereas the fractional rate of washout of intravascular 125 I-BSA decreased to less than one-half of baseline values (was prolonged 2-fold), and albumin permeation and mean-transit time were increased 3 and 5 times baseline, respectively. In hearts from diabetic rabbits, vascular resistance was similar to the control group before ischemia but increased only onethird as much during reflow after ischemia. Increases in LVEDP during reflow were -5 0 % lower than controls, and +dP/dt recovered -2.5 times more than in control hearts. 125 I-BSA permeation in diabetics was similar to controls before ischemia, but during reflow increased 6 times ( -2 times controls). Washout of intravascular 125 I-BSA was prolonged -2 0 % versus baseline during 3 h of reflow in hearts from diabetic rabbits. Thus, ALX-D in the rabbit delayed ischemiareperfusion injury to myocytes and vascular smooth muscle cells while increasing vascular albumin permeation. Diabetes 38:1484-91,1989 N umerous epidemiological studies have shown that cardiovascular disease is a major cause of morbidity and mortality in subjects with chronic diabetes. The mortality rate for diabetic subjects after myocardial infarction has been reported to be twice that of age-and sex-matched nondiabetic subjects (1,1 a,2), and the increased risk is present for both sexes and all ages, although the greatest risk is among younger subjects (2,3) and women (4). Although the increased mortality traditionally has been attributed to an accelerated development of coronary atherosclerosis, factors other than coronary artery disease, such as myocardial dysfunction, autonomic neuropathy, and coronary microangiopathy have also been suggested as important factors (5,6).Despite the vast literature on myocardial metabolism and mechanical performance in various animal models of diabetes (7-10), only a few studies have assessed effects of ischemia-reperfusion injury on ventricular function in these models (11)(12)(13)(14), and virtually no information is available on effects of diabetes on the response of the coronary vasculature to ischemia-reperfusion injury.These experiments were undertaken to assess coronary vascular hemodynamics, endothelial cell-barrier funct...

Ischemia-Reperfusion Increases Transfection Efficiency of Intracoronary Adenovirus Type 5 in Pig Heart In Situ

“…Several agents that increase vascular permeability have been shown to increase efficiency of gene transfer, such as sodium nitroprusside (SNP; Roth et al, 2004), nitroglycerin (NTG), vascular endothelial growth factor (VEGF; Nagata et al, 2001), substance P (Iwatate et al, 2003), and histamine (Greelish et al, 1999). In addition, ischemia reperfusion (I/R) also increases vascular permeability, thereby potentially increasing TE (Tilton et al, 1985(Tilton et al, , 1989). Low-level or transient ischemia increases the permeability/surface area ratio of the coronary vascular bed (Harris et al, 1984).…”