A simple technique for the reliable induction of coronary artery thrombosis in a conscious dog by delivery of low amperage electric current to the intimal surface of the artery io described. Ibuprofen, an agent known to inhibit platelet function and ptostaglandin synthesis is evaluated in this model. Comparison of myocardial infarct site, throabur weight, arrhythmia development and scanning electron nicrographs of drug treated and control animals indicate that Ibuprofen is capable of protecting against the deleterious effects of coronary artery thrombosis produced by this technique. This method holds considerable potential as an ;iD. vivq model of coronary artery thrombosis and one in which evaluation of anti-thrw botic agents is possible.

SUMMARY The hemodynamic and antithrombotic properties of prostacyclin (PGI2) were evaluated in an in vivo canine model in which left circumflex coronary artery (LCX) thrombus formation was initiated by electrical stimulation (150 iA, DC for 6 hours) of the artery's intimal surface via an implanted silver wire electrode. Eleven of the 12 control dogs (92%) developed totally occlusive LCX thrombi after an average of 3.2 + 0.4 hours of LCX stimulation; the remaining control dog underwent spontaneous ventricular fibrillation.A PGI2 infusion (150, 300 or 500 ng/kg/min) into the left atrial appendage was begun 10 minutes before the start of LCX stimulation and continued throughout the 6-hour stimulation period. LCX thrombus wet weight and the incidence of occlusive LCX thrombosis decreased in the PGI2-treated dogs in a dose-dependent manner. Hemodynamically, after 6 hours of PGIs infusion at 500 ng/kg/min, mean arterial pressure decreased by 36 ± 4%, cardiac output increased by 51 ± 14%, and the effect on heart rate was inconsistent. Light and scanning electron microscopic examination of the LCX at the site of electrode insertion in PGI2-treated dogs (500 ng/kg/min) revealed a damaged and denuded. intimal surface but no thrombi, in contrast to the thrombus formation in similar specimens taken from control dogs. In this report, we describe the potent hemodynamic effects of prolonged PGI2 infusion and demonstrate its ability to prevent coronary artery thrombosis in response to intimal injury.

Time-dependent changes in mitochondrial function and structure resulting from 1 hr of left circumflex coronary artery occlusion followed by 2 to 24 hr of reperfusion were examined. These changes were correlated with changes in myocardial ultrastructure, tissue water content, infarct size and mitochondrial calcium content. The heart was removed after different periods of reperfusion, and mitochondria were isolated from ischemic and nonischemic regions of the left ventricle. Tissue samples from ischemic and nonischemic myocardium also were taken for electron microscopy and tissue water content determinations. Infarct size was measured by the nitroblue tetrazolium staining method. Oxygen consumption by mitochondria isolated from ischemic and nonischemic myocardium was measured in vitro. Mitochondria from ischemic myocardium showed time-dependent decreases in rates of oxygen consumption and tightness of coupling. Electron microscopy revealed progressive ultrastructural deterioration in ischemic myocardium, including accumulation of calcium deposits within mitochondria, a finding corroborated by elevated concentrations of calcium in mitochondria isolated from the same area. Tissue wet-to-dry weight ratios were increased significantly in ischemic myocardium. A small, but significant, decrease in respiratory function was observed in mitochondria isolated from nonischemic myocardium several hrs after reperfusion; however, normal respiration was observed 24 hrs after release of occlusion. This latter observation indicates that the nonischemic zone also is affected by regional ischemia. The results obtained indicate that temporary left circumflex artery occlusion and reperfusion result in progressively decreasing mitochondrial function and structure within the ischemic myocardium, and that these changes are accompanied by cellular electrolyte alterations.

We have developed and employed a stereotaxic coordinate system for the pig brain based on eternal skull landmarks. Sagittal, coronal, and horizontal planes were defined. Based on histological maps and ventricular casts, the coordinates for locating the lateral ventricles were described. Guide tubes leading to the lateral ventricles have been chronically implanted. This access route to the ventricular system has been used for stimulation of the dipsogenic response with angiotensin and for withdrawal of cerebrospinal fluid. Solved and unsolved problems arising with these procedures have been defined.

Cat isolated hearts were perfused via the aorta with normothermic arterial blood from donor cats. After 1 hr of equilibration, dl-propranolol (1.9 mg/kg), atenolol (1.65 mg/kg), or physiological saline solution was infused via the aortic cannula. The hearts were made globally ischemic for 1 hr and reperfused for 1 hr. Hearts given saline but not made ischemic, and hearts from blood-donor cats served as controls. The hearts were flushed with physiological saline for 2 min, then perfused with cacodylate-buffered glutaraldehyde containing 1% LaQ. Samples of left ventricle were postfixed in osmium and prepared for electron microscopy. Microvessels in nonischemic tissues had heavy La3+ staining on luminal surfaces of endothelial cells. Many plasmalemmal vesicles along luminal surfaces of endothelial cells were filled with Las+. Several vesicles appeared to open onto both surfaces thus forming channels through the endothelium. Lanthanum penetrated into, and occasionally through, interendothelial junctions. Endothelial cells lining vessels in ischemic myocardium were swollen, had pale cytoplasm, and showed little La3+ on the luminal surfaces. Few plasmalemmal vesicles were present and the mitochondria contained deposits of Las+. Extravascular spaces were distended but interendothelial junctions seemed to be intact. Lanthanum staining and morphology of endothelial cells in hearts treated with propranolol or atenolol were very similar to nonischemic myocardium. The data suggest that the B-blocking agents, propranolol and atenolol, maintain the integrity of coronary vascular endothelium during ischemia.