Hours Of Permanent Occlusion Research Articles

Physiological basis for potassium (39K) magnetic resonance imaging of the heart.

The potassium cation (K+) is fundamentally involved in myocyte metabolism. To explore the potential utility of direct MRI of the most abundant natural isotope of potassium, 39K, we compared 39K magnetic resonance (MR) image intensity with regional myocardial K+ concentrations after irreversible injury. Rabbits were subjected either to 40 minutes of in situ coronary artery occlusion and 1 hour of reperfusion (n=26) or to 24 hours of permanent occlusion (n=4). The hearts were then isolated and imaged by 39K MRI (n=10), or tissue samples were analyzed for regional 39K content by MR spectroscopy (n=9), K+ and Na+ concentrations by atomic emission spectroscopy (inductively coupled plasma atomic emission spectroscopy; n=5), or intracellular K+ content by electron probe x-ray microanalysis (n=6). Three-dimensional 39K MR images of the isolated hearts were acquired in 44 minutes with 3 x 3 x 3-mm resolution. 39K MR image intensity was reduced in infarcted regions (51.7+/-4. 8% of remote; P<0.001). The circumferential extent and location of regions of reduced 39K image intensity were correlated with those of infarcted regions defined histologically (r=0.97 and r=0.98, respectively). Compared with remote regions, tissue analysis revealed that infarcted regions had reduced 39K concentration (by MR spectroscopy, 40.5+/-9.3% of remote; P<0.001), reduced potassium-to-sodium ratio (by inductively coupled plasma atomic emission spectroscopy, 20.7+/-2.1% of remote; P<0.01), and reduced intracellular potassium (by electron probe x-ray microanalysis, K+ peak-to-background ratio 0.95+/-0.32 versus 2.86+/-1.10, respectively; P<0.01). We acquired the first 39K MR images of hearts subjected to infarction. In the pathophysiologies examined, potassium (39K) MR image intensity primarily reflects regional intracellular K+ concentrations.

Hyperglycemia and the vascular effects of cerebral ischemia.

A well-demarcated infarct was observed after 4 hours of rat middle cerebral artery (MCA) occlusion with xylazine/ketamine but not pentobarbital or isoflurane anesthesia. This study examined whether this reflected vascular changes and, because xylazine induces hyperglycemia, whether glucose could cause similar vascular effects in cerebral ischemia. To examine the effects of anesthetics, rats were anesthetized for thread occlusion of the MCA with either xylazine/ketamine, pentobarbital, or isoflurane. To evaluate the effects of glycemia, acute hyperglycemia was induced by glucose injection. In both experiments, cerebral plasma volume (CPV) was determined using 3H-inulin after 4 hours of permanent occlusion, and cerebral blood flow was measured using [14C]iodoantipyrine following 2 hours of reperfusion after 2 or 4 hours of occlusion. The presence of cerebral hemorrhage after reperfusion was checked macroscopically and infarct volume with 2,3,5-triphenyltetrazolium staining. The ischemic CPV was about 50% of the contralateral values with xylazine/ketamine but not with the other anesthetics. On reperfusion, ischemic cerebral blood flow with xylazine/ketamine anesthesia was approximately half that with pentobarbital. Use of xylazine/ketamine also resulted in more frequent hemorrhagic infarcts and a larger infarct volume. Induced hyperglycemia resulted in a CPV decrease in the ischemic compared with nonischemic tissue (4.0 +/- 0.5 versus 7.4 +/- 0.2 microL/g; P < .001). Hyperglycemia also caused poor reperfusion and increased the occurrence of hemorrhagic infarction (hyperglycemia, 15 of 20; normoglycemia, 1 of 11; P < .01). Hyperglycemia induces marked cerebrovascular changes, both during ischemia and during reperfusion, that may exacerbate tissue damage. Change in CPV during ischemia may be a useful clinical indicator in predicting poor hemodynamic recovery and occurrence of hemorrhagic infarction after reperfusion therapy.

Effects of hyperglycemia on cerebral blood flow and edema formation after carotid artery occlusion in Fischer 344 rats.

This study examines whether during bilateral carotid artery occlusion in Fischer 344 rats, hyperglycemia induces cerebrovascular changes that enhance brain edema formation. Preischemic hyperglycemia was induced by intraperitoneal administration of D-glucose solution. Laser-Doppler flowmetry, indicated that after the initial decline in blood flow with carotid occlusion (36 +/- 4% of preischemic), hyperglycemic but not control rats showed a further progressive decrease to 19 +/- 2% of preischemic at 120 minutes (p < 0.001). Brain water content was significantly higher in hypercompared to normoglycemic rats after both 2 hours of permanent occlusion (3.86 +/- 0.05 vs. 3.73 +/- 0.03 g/g dry wt.; p < 0.05) and 2 hours of temporary occlusion followed by 1 hour of reperfusion (4.01 +/- 0.08 vs. 3.71 +/- 0.03 g/g dry wt.; p < 0.05). The difference in brain edema formation between normo- and hyperglycemic rats appears to primarily reflect the effects of hyperglycemia on CBF. Cerebral plasma volume (CPV) 2 hours after occlusion was also reduced in hyper-compared to normoglycemic rats (3.9 +/- 0.9 and 7.2 +/- 0.1 microliters/g; p < 0.01). Thus, hyperglycemia in a model of global ischemia induces a reduction in CPV and progressive decline in CBF. In this model, the decline in CBF is of sufficient magnitude to enhance brain injury as evidenced by edema formation.

Time course of infiltration and distribution of neutrophils following coronary artery reperfusion in the rat

To investigate the effect of coronary artery reperfusion on neutrophil infiltration into the myocardium in a model of low-collateral blood flow, we studied hearts from five groups of anesthetized rats subjected to 1) permanent coronary occlusion for 2 hours, 2) permanent coronary occlusion for 3 hours. 3) 1 hour of occlusion followed by reperfusion for 1 hour, 4) 1 hour of occlusion followed by reperfusion for 2 hours, or 5) sham operation Sections from hearts were examined microscopically (=750 fields/section), the neutrophils counted, and their location determined. Reperfusion for 1 hour did not increase the number of neutrophils compared to 2 hours of permanent occlusion (80 ± 17/section vs 59 ± 16/section, P = NS. However, 2 hours of reperfusion significantly increased the number of neutrophils (529 ± 128/section) compared to either 1 hour of reperfusion (80 ± 17/section, P < 0.001) or 3 hours of permanent occlusion (121 ± 25/section, P< 0.01). The distribution of neutrophils changed over time: after 1 hour of reperfusion, neutrophils were located primarily in vessels (74% ± 5%), but after 2 hours, only 32% ± 6% were in vessels, with most neutrophils located within the interstitium or in myocytes. Neutrophils appeared to enter the tissue via the subepicardial vessels and stream toward the subendocardium. We conclude that neutrophils are initially located in vessels: by 2 hours of reperfusion, however, they are located mainly in the interstitium and in myocytes. Reperfusion greatly increased the number of neutrophils in the heart compared with permanent occlusion; however, the increase did not occur until after 2 hours of reperfusion.

Limitation of myocardial infarct size by superoxide dismutase as an adjunct to reperfusion after different durations of coronary occlusion in the pig.

Superoxide dismutase (SOD) has been documented to limit myocardial infarct size in the richly collateralized dog heart. This study was designed to explore this concept in a low-collateralized animal model. A blind, randomized, placebo-controlled protocol was used in 65 pentobarbital-anesthetized pigs subjected to closed-chest left anterior descending coronary artery occlusion for 30 (n = 22), 60 (n = 22), and 90 (n = 14) minutes followed by reperfusion up to 24 hours from the start of occlusion. Another seven control pigs were subjected to 24 hours of permanent occlusion. A total dose of 9 mg/kg bovine CuZn SOD was administered as a bolus injection immediately before reperfusion followed by a 1-hour infusion. Infarct size was assessed by tetrazolium staining. Myocardium at risk and collateral flow were determined by using cerium-141-labeled microspheres (15 microns) during the occlusion. After 30 minutes of occlusion, infarct sizes in placebo versus SOD-treated animals were 45.5 +/- 15.7% vs. 23.8 +/- 15.6% of myocardium at risk (p = 0.007). The corresponding values after 60 minutes of occlusion were 78.6 +/- 9.3% vs. 66.9 +/- 14.6% (p = 0.035). SOD administered after 90 minutes of occlusion did not limit infarct size (88.5 +/- 4.8% vs. 92.3 +/- 5.2%). Twenty-four hours of coronary occlusion resulted in infarction of 92.4 +/- 4.2% of myocardium at risk. (All values are mean +/- SD.) Ventricular fibrillation occurred in only nine pigs distributed equally between SOD and placebo. The results indicate that CuZn SOD has the potential to further improve the myocardial salvage established by reperfusion of an ischemic pig heart territory. However, the narrow time window for limiting infarct size in the pig by reperfusion is not much extended by SOD.