- Email: [email protected]
Vascular changes in acutely ischemic muscle: an electron microscopic study
310
Abstracts
blood flow rates was extremely difficult. Utilizing a new system for converting the optical fluoroscopic image into an electronic signal and employing simple dye-dilution theory, acceptably accurate determinations of rates of blood flow can be made in any artery suitable for selective catheterization. Important information related to hypertension can now be obtained from selective renal arteriograms without modifying the usual anatomic study. Theoretically, this technic can be used to determine cardiac output. Using the television system as a sampling device, the dilution of radiographic contrast material following injection can be computed and the flow rate within the vessel determined. Accuracy of the order of 10 to 15% can be expected. A computer program is being developed to aid in the evaluation of coronary arterial disease. The measurement requires no change in the technics of the arterial visualization utilized by most departments. Vascular Changes in Acutely Ischemic Muscle: An Electron Microscopic Study. P. E. STROCK,Harvard Medical School, Boston, Mass. When flow is restored to cardiac muscle after ischemia, vascular tracers demonstrate an obstruction in the fine vessels of the myocardium. After ischemia similar obstructions develop in other organ systems, including skeletal muscle. To gather the precise data on flow in the microvasculature following ischemia, the fine vessels of skeletal muscle were studied after tourniquet ischemia of the rat hind limb. Obstruction occurs during the first 30 minutes after return of flow and persists for several hours. An ultrastructural search of the fine vessels was undertaken for morphologic obstacles and their possible relation to functional disturbance. Samples of tibia/is anterior muscle were taken 2, 10 and 30 minutes after release of a rubber band tourniquet (2 l/2 hours), fixed in 3% gluteraldehyde and prepared for electron microscopy. These studies demonstrated that (1) the injury following ischemia (vascular as well as parenchymal) was extremely focal, and (2) the areas of injury were not consistently related to areas of reflow or no-reflow. Changes consistent with injury were noted in (1) endothelium (swelling of intracellular organelles) ; (2) the intravascular compartment (swelling of the
formed elements of the blood); (3) the interstitial space (appearance of free blebs) ; and (4) the muscle fibers (swelling of intracellular organelles) . The lack of consistent structural damage to the vessels adequate to impair flow suggests the obstacle to reflow may be of a functional nature. A list of 13 structural or functional alterations that might contribute to impair reflow at the level of the microcirculation is discussed. Metabolic Effects of Ouabain in Dogs. L. TRINER, J. PAPAYOANOU,I’. KILHAN and G. G. NAHAS, College of Physicians and Surgeons of Columbia University, New York, N. Y. Ouabain in intact dogs ( 1.0 pg./kg./min. infused intravenously for 60 minutes) caused significant decreases in levels of plasma glycerol (-55y0 ) and glucose (-30~o) and also inhibited the metabolic effects of epinephrine (0.8 pg./kg./min. for 30 minutes); glucose release was decreased by 24%, glycerol by 57% and free fatty acids by 67%. Ouabain combined with insulin or propranolol caused a greater and more prolonged decrease in blood glucose levels than any of the drugs administered separately. In intact dogs, ouabain changed significantly portohepatic venous differences in plasma glucose and K+ (from +6.6 to -13.6 mg./lOO ml. and from -0.03 to -0.4 mEq./L., respectively), thus indicating an increase of glucose and K+ uptake by the liver. By contrast, in animals that had undergone pancreatectomy, ouabain did not cause any significant decrease in peripheral glucose level, and the portohepatic differences in plasma glucose and K+ changed from +5.3 to +30.2 mg./lOO ml. and from -0.01 to +0.2 mEq./L., respectively. These changes, indicating an increased release of glucose and K+ by the liver in dogs after pancreatectomy, were also observed in isolated rat liver perfused with ouabain, lO_sM. Glucose uptake of the hind limb increased significantly during the infusion of ouabain in normal dogs but did not change in the dogs after pancreatectomy. In intact dogs, ouabain caused a significant increase in plasma insulin levels in portal blood (+125%) and a smaller, although consistent, increase in insulin levels in peripheral blood (+770/,). These results demonstrate that the observed metabolic effects of ouabain in the dog are mainly mediated by insulin.
THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Abstracts
blood flow rates was extremely difficult. Utilizing a new system for converting the optical fluoroscopic image into an electronic signal and employing simple dye-dilution theory, acceptably accurate determinations of rates of blood flow can be made in any artery suitable for selective catheterization. Important information related to hypertension can now be obtained from selective renal arteriograms without modifying the usual anatomic study. Theoretically, this technic can be used to determine cardiac output. Using the television system as a sampling device, the dilution of radiographic contrast material following injection can be computed and the flow rate within the vessel determined. Accuracy of the order of 10 to 15% can be expected. A computer program is being developed to aid in the evaluation of coronary arterial disease. The measurement requires no change in the technics of the arterial visualization utilized by most departments. Vascular Changes in Acutely Ischemic Muscle: An Electron Microscopic Study. P. E. STROCK,Harvard Medical School, Boston, Mass. When flow is restored to cardiac muscle after ischemia, vascular tracers demonstrate an obstruction in the fine vessels of the myocardium. After ischemia similar obstructions develop in other organ systems, including skeletal muscle. To gather the precise data on flow in the microvasculature following ischemia, the fine vessels of skeletal muscle were studied after tourniquet ischemia of the rat hind limb. Obstruction occurs during the first 30 minutes after return of flow and persists for several hours. An ultrastructural search of the fine vessels was undertaken for morphologic obstacles and their possible relation to functional disturbance. Samples of tibia/is anterior muscle were taken 2, 10 and 30 minutes after release of a rubber band tourniquet (2 l/2 hours), fixed in 3% gluteraldehyde and prepared for electron microscopy. These studies demonstrated that (1) the injury following ischemia (vascular as well as parenchymal) was extremely focal, and (2) the areas of injury were not consistently related to areas of reflow or no-reflow. Changes consistent with injury were noted in (1) endothelium (swelling of intracellular organelles) ; (2) the intravascular compartment (swelling of the
formed elements of the blood); (3) the interstitial space (appearance of free blebs) ; and (4) the muscle fibers (swelling of intracellular organelles) . The lack of consistent structural damage to the vessels adequate to impair flow suggests the obstacle to reflow may be of a functional nature. A list of 13 structural or functional alterations that might contribute to impair reflow at the level of the microcirculation is discussed. Metabolic Effects of Ouabain in Dogs. L. TRINER, J. PAPAYOANOU,I’. KILHAN and G. G. NAHAS, College of Physicians and Surgeons of Columbia University, New York, N. Y. Ouabain in intact dogs ( 1.0 pg./kg./min. infused intravenously for 60 minutes) caused significant decreases in levels of plasma glycerol (-55y0 ) and glucose (-30~o) and also inhibited the metabolic effects of epinephrine (0.8 pg./kg./min. for 30 minutes); glucose release was decreased by 24%, glycerol by 57% and free fatty acids by 67%. Ouabain combined with insulin or propranolol caused a greater and more prolonged decrease in blood glucose levels than any of the drugs administered separately. In intact dogs, ouabain changed significantly portohepatic venous differences in plasma glucose and K+ (from +6.6 to -13.6 mg./lOO ml. and from -0.03 to -0.4 mEq./L., respectively), thus indicating an increase of glucose and K+ uptake by the liver. By contrast, in animals that had undergone pancreatectomy, ouabain did not cause any significant decrease in peripheral glucose level, and the portohepatic differences in plasma glucose and K+ changed from +5.3 to +30.2 mg./lOO ml. and from -0.01 to +0.2 mEq./L., respectively. These changes, indicating an increased release of glucose and K+ by the liver in dogs after pancreatectomy, were also observed in isolated rat liver perfused with ouabain, lO_sM. Glucose uptake of the hind limb increased significantly during the infusion of ouabain in normal dogs but did not change in the dogs after pancreatectomy. In intact dogs, ouabain caused a significant increase in plasma insulin levels in portal blood (+125%) and a smaller, although consistent, increase in insulin levels in peripheral blood (+770/,). These results demonstrate that the observed metabolic effects of ouabain in the dog are mainly mediated by insulin.
THE
AMERICAN
JOURNAL
OF CARDIOLOGY