Hyaluronidase does not prevent deterioration of vascular functional integrity during reperfusion after no-flow ischemia in isolated rabbit hearts.

Tilton, Ronald G.; Cole, Peter A.; Larson, Kenneth B.; Kilo, Charles; Williamson, John

doi:10.1161/01.res.56.6.839

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…The decreased flow rate may be due to contracture of arterial vascular smooth muscle as suggested by previous observations (15,41) or to myocyte contracture, which could compress vessels (discussed below). In addition, the ischemia-induced increase in interstitial water content can be prevented with hyaluronoglucuronidase treatment, whereas the vascular resistance changes are only partially ameliorated (45). Interstitial edema is an unlikely explanation for the increased vascular resistance (and LVEDP), because the water content of diabetic hearts was increased significantly over controls, yet vascular resistance and LVEDP were significantly lower than control values during reflow.…”

Section: Discussionmentioning

confidence: 98%

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

et al. 1989

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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...

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Section: Discussionmentioning

confidence: 98%

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

et al. 1989

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“…At present, we are unable to explain the graft blood flow‐reducing properties of hyaluronidase after experimental pancreas transplantation. The concept that a diminished HA content decreases oedema and intra‐graft pressure in transplants [24, 25] as well as tumours [26–28], and thereby affects blood flow is not sufficient in view of the similar effects in the endogenous pancreas, despite a less pronounced pancreatitis and the lack of effect on HA content by the hyaluronidase treatment in this gland. Our findings therefore suggest that hyaluronidase causes the blood flow decrease by another mechanism than degradation of HA within the pancreas.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronidase Treatment of Graft Pancreatitis in Rats: Marked Effects on the Blood Perfusion of the Transplanted Pancreas

Jansson

Tufveson

Bodin

et al. 2010

Scandinavian Journal of Immunology

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Hyaluronan is known to accumulate in tissues during inflammatory diseases associated with graft implantation and rejection of organ allografts. The aim was to evaluate whether hyaluronidase treatment affected hyaluronan content and blood perfusion in graft pancreatitis. Syngeneic rat pancreatic‐duodenal transplantations were performed. Two days later blood flow measurements were made with a microsphere technique in both grafted and endogenous pancreas in animals treated with daily injections of vehicle or hyaluronidase (20.000 U/kg). Non‐transplanted rats served as controls. Also, samples for analysis of hyaluronan and water content were taken. The hyaluronan content of the pancreatic graft was increased after transplantation. Hyaluronidase treatment markedly reduced total pancreatic and islet blood flow in both grafted and endogenous pancreas, whereas duodenum blood flow was unaffected. No blood flow effects were seen in non‐transplanted control rats. Hyaluronan content was increased in the grafted pancreas, but hyaluronidase treatment decreased it to levels comparable to those of the endogenous gland. There were no differences in hyaluronan content in the endogenous pancreases of transplanted and non‐transplanted rats. Graft pancreatitis after rat pancreas transplantation is associated with an increased hyaluronan content, which can be reduced by treatment with hyaluronidase. Hyaluronidase treatment of the graft recipients effected a 50% reduction in total pancreatic and islet blood flow in the graft, as well as in the endogenous pancreas. The functional importance of this is at present unknown.

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“…Studies of myocardial protection from ischemic damage have focused primarily on the myocyte (Bittl and Shine, 1983;Jolly et al, 1984;McDonagh et al, 1984b); however, other studies have reported microvascular protection with propranolol (Kloner et al, 1977;Haack et al, 1981), mannitol (Willerson et al, 1972;Fabiani, 1976;Powell et al, 1976;Powers et al, 1984), and allopurinol (Fabiani, 1976), but not with hyaluronidase (Tilton et al, 1985). Microvascular protection is considered to be important because, when severe microvascular damage occurs, a permeability edema may develop, and myocardial enzymes are free to diffuse and wash out of the heart.…”

Section: Maintenance Of Microvascular Integritymentioning

confidence: 99%

Prevention of transcoronary macromolecular leakage after ischemia-reperfusion by the calcium entry blocker nisoldipine. Direct observations in isolated rat hearts.

McDonagh¹,

Roberts²

1986

Circulation Research

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Coronary microvascular damage appears to play a role in reperfusion injury after myocardial ischemia. This study was designed to afford direct viewing of the effects of myocardial ischemia-reperfusion on the coronary microcirculation and to determine whether pretreatment with the calcium blocker nisoldipine would attenuate any microvascular damage during reperfusion. Four groups of isolated rat hearts were perfused with a solution that contained red cells and fluorescent albumin, but was essentially free of platelets and leukocytes. Group I served as a nonischemic control. Group II hearts were subjected to 30 minutes of no-flow ischemia followed by reperfusion. Group III hearts were pretreated with nisoldipine (1 microgram/min) for 5 minutes before ischemia, and group IV hearts were treated with nitroglycerin (93 micrograms/min) before and after ischemia to mimic the vasodilation caused by nisoldipine. Perfused coronary capillarity and transcoronary extravasation of plasma albumin were measured by direct visualization techniques before and after ischemia. For group I, there was no significant change in coronary resistance, perfused capillarity, or transcoronary extravasation with time. For both groups II and IV, ischemia-reperfusion caused no increase in coronary resistance, but a significant decrease in perfused capillarity and a marked increase in transcoronary extravasation of fluorescent albumin (P less than 0.05). The nisoldipine group (group III) demonstrated a similar decrease in perfused capillarity but no increase in protein extravasation during reperfusion. These results indicate that, in the heart, platelets and/or leukocytes are not absolutely necessary to induce either the no-reflow phenomenon or the permeability damage observed during reperfusion after ischemia. The protective effect of treatment with nisoldipine appeared to be independent of vasodilation. We speculate that this calcium blocker reduced endothelial uptake of calcium during reperfusion, preventing endothelial deformation and formation of interendothelial gaps.

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Hyaluronidase does not prevent deterioration of vascular functional integrity during reperfusion after no-flow ischemia in isolated rabbit hearts.

Cited by 5 publications

References 43 publications

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

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

Hyaluronidase Treatment of Graft Pancreatitis in Rats: Marked Effects on the Blood Perfusion of the Transplanted Pancreas

Prevention of transcoronary macromolecular leakage after ischemia-reperfusion by the calcium entry blocker nisoldipine. Direct observations in isolated rat hearts.

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