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Biomedical subjects

E Corday

Publications and source records attributed to E Corday.

At least 37 records · Page 2Linked to original sources

Ischemic brain rescue by transvenous perfusion in baboons with venous sinus occlusion.

We studied brain retroperfusion in nine adult baboons. Experiments in four baboons determined techniques and the safety of retroperfusion, and experiments in three baboons determined the ability of retroperfusion to reverse cerebral ischemia. Two baboons died before retroperfusion. Arterial blood was continuously circulated by an external pumping system from one femoral artery into the intracranial sinuses through specially designed balloon-tipped catheters placed percutaneously into the sigmoid sinuses bilaterally. The balloons intermittently occluded the sinuses. Ischemia was produced by occluding the left middle cerebral artery. Standard and computed electroencephalography with topographic mapping monitored the onset and reversal of ischemia. Retroperfusion rate exceeded 50 ml/min with a mean intrasinus pressure increase of 27 (0-149) mm Hg in all seven experiments. Venograms demonstrated complete or partial filling of the superior sagittal sinus in each experiment. Four experiments without ischemia established maximal balloon occlusion cycles, retroperfusion rates, and sinus pressure changes. These four baboons were neurologically normal after retroperfusion; two had normal magnetic resonance imaging scans. Ischemic changes, detected by electroencephalography following middle cerebral artery occlusion, were reversed with retroperfusion in all three ischemia experiments. Autopsies in the seven baboons demonstrated no parenchymal hemorrhage or edema. Our results suggest that further investigation of retroperfusion, and possibly retroinfusion of agents for cerebral protection, is warranted.

Animals↗

Overestimation of myocardial infarct size by histologic measurement in a model of occlusion followed by reperfusion.

We studied 32 transverse left ventricular slices of myocardium from 16 pigs after 45 to 100 minutes of coronary artery occlusion followed by 180 minutes of reperfusion. Infarct area for each slice was determined as follows: (1) grossly, by triphenyl tetrazolium chloride staining of each slice, and (2) microscopically, by complete histologic sectioning of the triphenyl tetrazolium chloride-stained surface of each slice. Planimetry of necrotic and nonnecrotic areas was performed from tracings and photographs of triphenyl tetrazolium chloride-stained slices and from actual histologic sections. When triphenyl tetrazolium chloride and histologic measurements were compared, necrotic tissue area had decreased 11.4% +/- 15.0% (2.59 +/- 1.04 vs 2.09 +/- 0.86 cm2). Nonnecrotic tissue area decreased 20.6% +/- 24.0% (8.31 +/- 3.79 vs 5.16 +/- 2.73 cm2). In this model of ischemia followed by reperfusion, with fixation and processing, viable tissue shrank almost twice as much as necrotic tissue. This differential shrinkage introduces an error resulting in overestimation of infarct size by histologic quantitation.

Animals↗

Beneficial effects of coronary venous retroinfusion of superoxide dismutase and catalase on reperfusion arrhythmias, myocardial function, and infarct size in dogs.

The efficacy of coronary venous retroinfusion of superoxide dismutase and catalase was studied in anesthetized closed chest dogs with 90-min left anterior descending coronary artery (LAD) occlusion followed by 3-h reperfusion. In group A, superoxide dismutase (2.5 mg/kg) and catalase (2.5 mg/kg) were administered by a 30-min continuous right atrial infusion beginning 15 min before reperfusion and supplemented by a bolus injection of superoxide dismutase (2.5 mg/kg) and catalase (2.5 mg/kg) through the great cardiac vein immediately before reperfusion. The treatment in group B was similar to that in group A, except that the bolus injection was into the right atrium. In the control group (group C), saline was administered in the same manner as in group A. Infarct size, expressed as a percentage of the risk area, was significantly smaller in group A (11.3 +/- 8.9%) than in groups B (31.3 +/- 21.1%) and C (43.0 +/- 16.9%; p less than 0.05). Regional function of the ischemic zone measured by two-dimensional echocardiography exhibited significantly (p less than 0.05) greater recovery after 3-h reperfusion in group A (30.3 +/- 8.4%) versus groups B (12.5 +/- 13.7%) and C (12.1 +/- 11.7%). Moreover, there were significantly fewer postreperfusion ventricular arrhythmias in group A as compared with groups B and C. The results of this study indicate that coronary venous retroinfusion is an effective method for delivery of superoxide dismutase and catalase.

Animals↗

Sequential noninvasive assessment of left ventricular size, regional wall thickness and function during 3 hours of coronary artery occlusion and reperfusion: differential effects of reflow in dogs with small vs large areas at risk.

1. The present study was undertaken to determine noninvasively the sequential changes in left ventricular (LV) size, wall thickness and regional contractile function occurring during 3 h of proximal left anterior descending coronary artery occlusion (CAO), and their modification by reperfusion (REP) over a 7-day period. 2. Twenty, closed-chest, anesthetized dogs underwent CAO for 3 h and were reperfused for 7 days. Hemodynamics (aortic, LV pressure, LV dP/dt) and regional LV function were measured sequentially during CAO and reperfusion. The animals were killed at 7 days and infarct size was measured using the triphenyl-tetrazolium-chloride technique. Regional function (systolic fractional area change, FAC) was measured in 40 LV segments of 5 two-dimensional echo short-axis planes (8 segments per section). 3. At three hours of CAO, 14 dogs developed extensive areas of akinesis or dyskinesis in more than 6 segments (Group I, large risk area), whereas 6 dogs developed akinesis or dyskinesis in 6 segments or less (Group II, small risk area). Four dogs died between 12 and 48 h after REP in Group I and none of Group II died. Recovery of regional function after REP was significantly different between Groups I and II: in hypokinetic segments, FAC improved from 16.7 +/- 0.9% (mean +/- SEM) at 3 h of CAO to 25.4 +/- 3.2% at 24 h and to 34.9 +/- 2.0% at 7 days (66.3 +/- 3.4% of baseline) after REP in Group I; in Group II, FAC increased from 16.6 +/- 1.5% at 3 h of CAO to 48.5 +/- 7.4% at 24 h and to 52.4 +/- 1.6% (92.7 +/- 2.8% of baseline) at 7 days after REP. In akinetic/dyskinetic segments, FAC increased from -9.2 +/- 2.4% at 3 h of CAO to 8.2 +/- 2.6% at 72 h and to 8.3 +/- 3.2% (15.1 +/- 5.8% of baseline) at 7 days of REP in Group I; in Group II, FAC rose significantly from -7.6 +/- 1.6% at 3 h of CAO to 39.9 +/- 7.3% at 24 h and to 50.8 +/- 4.3% (89.2 +/- 4.9% of baseline) at 7 days after REP. There was a significant inverse correlation between the magnitude of compensatory hyperkinesis in the nonischemic wall and the extent of hypokinesis at 60 min (r = -0.82, P less than 0.001), but this correlation was less significant at 24 h (r = -0.64, P less than 0.01), 72 h (r = -0.53, P less than 0.02), and 7 days (r = -0.50, P less than 0.05) after REP.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

The pattern of delivery and distribution of coronary venous retroinfusate in canine hearts.

The delivery and distribution of retroinfusate premixed with radionuclide microspheres (15 microns) in the coronary venous system of canine hearts was studied in in vitro and in vivo experiments. Results showed that about 51-85% of the retroinfusate was shunted directly by vessels greater than 15 microns in diameter to the right heart in cases of isolated heart study, while the remaining 21-42% passed through intramyocardial capillaries with obvious nutritional effects. In the closed-chest experiments, 95% of the retroinfusate was bypassed to the right heart; less than 5% went through the intramyocardial microcirculation system. Intramyocardial distribution pattern of the retroinfusate indicated a predominant supply to the left ventricular free wall. There was a preferential distribution of the retroinfusate to the ischemic area with a subendo subepi blood flow ratio of up to 1.79 +/- 0.21 post-LAD occlusion.

Animals↗

Echocardiographic criteria to distinguish reversible from irreversible myocardial ischaemia.

This treatise reviews two-dimensional echocardiographic criteria which have been developed to describe and distinguish reversible vs irreversible myocardial ischaemia. It also discusses the new pathophysiologic concepts such as 'hibernating' and 'decapitated' myocardium, and also 'reperfusion injury' and 'stunned' myocardium, complications which may supervene following reperfusion of jeopardized ischaemic myocardium. Computerized regional and global wall-motion analysis is now usually measured from enhanced endocardial edges. Provocative interventions can contribute information regarding viability of jeopardized ischaemic regions by testing contractile response of the myocardium to afterload reducing agents such as nitroglycerine or nitroprusside. They can also validate viability by demonstrating that post-extrasystolic beats can still cause potentiation. Ultrasonic contrast washout half-life of the myocardium which is compromised by stenotic coronary arteries provides a promising method for supplying information about the coronary perfusion defects and flow reserve. The decrease in global or regional ejection fraction following exercise echocardiography may show if jeopardized ischaemic myocardium is irreversibly damaged. A new hypercontractility phenomenon is described following brief coronary occlusions such as during percutaneous transluminal angioplasty, or after sudden release of angiospasm, and this should be considered a sign of viability. Increase in end-diastolic wall thickness and echo amplitudes immediately after reperfusion of ischaemic segments is often associated with reversibly damaged myocardium.

Coronary Disease↗

Enhanced myocardial washout and retrograde blood delivery with synchronized retroperfusion during acute myocardial ischemia.

The effects of synchronized coronary venous retroperfusion of arterial blood on myocardial washout were studied with digital subtraction angiography in 10 closed chest dogs during balloon occlusion of the proximal left anterior descending coronary artery. The center lumen of the intracoronary balloon catheter was used for sequential injections of 1 ml (meglumine diatrizoate) Renografin-76, and contrast washout rate was determined by videodensitometry in myocardial regions subserved by the left anterior descending coronary artery. Before coronary artery occlusion, washout rate was 22.4 +/- 2.7 min-1 (mean +/- SEM). Five minutes after occlusion, and immediately before synchronized retroperfusion, washout rate dropped sharply to 2.0 +/- 0.7 min-1. Twenty-five minutes after occlusion, with 50 ml/min synchronized retroperfusion treatment applied for 5 minutes, washout rate was 5.0 +/- 1.5 min-1. Thus, synchronized retroperfusion significantly (p less than 0.05) accelerated contrast disappearance over that during presynchronized retroperfusion ischemia. To determine the effects of synchronized retroperfusion on retrograde delivery to the ischemic myocardium, monastral blue dye was retroinfused through the system into the great cardiac vein before the dog was killed. Transverse heart slices were then studied by light microscopy, and regional intravascular dye content was scored from 0 to 3 (0 = no dye, 3 = maximal dye). After great cardiac vein synchronized retroperfusion, blue dye content in capillaries of ischemic anterior and nonischemic posterior aspects of the left ventricle was 2.3 +/- 0.5 versus 0.7 +/- 0.3, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Effects of intracoronary infusion of arterial blood or Fluosol-DA 20% on regional myocardial metabolism and function during brief coronary artery occlusions.

Effects of intracoronary infusion (50 ml/min) of arterial blood, oxygenated or unoxygenated Fluosol, or Plasmalyte A on hemodynamics, electrocardiogram, regional myocardial function, and lactate metabolism were studied in six closed-chest dogs during 2 min occlusions of the left anterior descending coronary artery followed by 10 min of reperfusion. Normal hemodynamics were maintained with infusion of arterial blood and oxygenated Fluosol, whereas unoxygenated Fluosol and Plasmalyte A resulted in hemodynamic deterioration similar to that noted with no treatment. Ischemic zone systolic fractional area change, an index of systolic function measured by two-dimensional echocardiography, remained normal during the occlusion supplemented with intracoronary arterial blood (49 +/- 7%), was moderately hypokinetic with oxygenated Fluosol (31 +/- 10%), and became severely hypokinetic with unoxygenated Fluosol (14 +/- 14%), with Plasmalyte A (2 +/- 13%), and in the absence of treatment (5 +/- 9%). Only infusion of arterial blood resulted in no ST segment elevation or lactate production. Thus intracoronary infusion of arterial blood during brief coronary occlusion maintained normal myocardial function and aerobic metabolism. Infusion of oxygenated Fluosol resulted in amelioration of the decline in regional function after coronary occlusion, but not complete protection.

Angioplasty, Balloon↗

Coronary venous retroinfusion of procainamide: a new approach for the management of spontaneous and inducible sustained ventricular tachycardia during myocardial infarction.

The efficacy of retrograde coronary venous delivery of procainamide for the management of spontaneous and inducible sustained ventricular tachycardia was evaluated and compared with systemic intravenous procainamide administration in 22 conscious dogs with permanent left anterior descending coronary artery occlusion. Selective retrograde injection of procainamide was achieved through an autoinflatable balloon catheter placed in the great cardiac vein, with the tip positioned in the vicinity of the site of left anterior descending coronary occlusion. Great cardiac vein retroinfusion of procainamide was significantly (p less than 0.05) more effective than systemic intravenous injection against spontaneous ventricular tachycardia 1 day after coronary artery occlusion (13 dogs) and against electrically induced sustained ventricular tachycardia in the 3 to 12 day postocclusion period (9 dogs). Significantly lower doses of procainamide were used with retroinfusion as compared with systemic administration, that is, 19.6 +/- 8.8 versus 35 +/- 0 mg/kg body weight during spontaneous tachycardia and 13.4 +/- 4.1 versus 32.1 +/- 2 mg/kg during induced tachycardia (p less than 0.01). Retroinfusion of saline solution through the great cardiac vein had no effect on either type of tachycardia. Myocardial tissue procainamide levels measured in infarcted and ischemic zones of the left anterior ventricular wall were 9 to 100 times higher after great cardiac vein retroinfusion than after systemic injection. Great cardiac vein dye injection studies demonstrated a preferential distribution in left ventricular regions supplied by the occluded coronary artery. It is concluded that regional coronary venous procainamide retroinfusion in dogs with myocardial infarction is more effective than systemic intravenous injection against both spontaneous and inducible sustained ventricular tachycardia. The greater efficacy of great cardiac vein treatment appears to be primarily related to selectively increased delivery of procainamide to ischemic myocardial sites.

Animals↗

Effects of staged versus sudden reperfusion after acute coronary occlusion in the dog.

Sudden and staged reperfusion after experimental coronary artery occlusion was studied in relation to recovery of cardiac function and postreperfusion arrhythmias. Eighteen closed chest dogs with 3 hour intracoronary balloon occlusion of the proximal left anterior descending coronary artery were studied using two-dimensional echocardiography over a period of 3 weeks after reperfusion. Nine dogs had sudden reperfusion by abrupt balloon deflation. In nine other dogs reperfusion was staged with partial reflow (20 ml/min) for 2 hours through the central lumen of the catheter during persisting intracoronary balloon inflation, followed by balloon deflation and full reperfusion. Within the first 30 minutes of sudden reperfusion, ischemic zone end-diastolic wall thickness increased significantly, from 6.8 +/- 0.3 mm at 3 hours of occlusion to 10.2 +/- 2.6 mm (p less than 0.05). In contrast, at 30 minutes of partial reflow, wall thickness was 7.5 +/- 0.7 versus 6.8 +/- 0.7 mm at 3 hours of occlusion (NS). A small temporary increase in end-diastolic wall thickness was noted when full reflow was established after 2 hours of staged reperfusion. However, wall thickness was normal on the first day in the staged reperfusion series, while sudden reperfusion delayed recovery to 7 days. Function of the ischemic zone failed to improve substantially until day 3 after sudden reperfusion, whereas it improved consistently starting as early as 30 minutes after institution of the staged reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Digital angiographic measurement of radiographic contrast material kinetics for estimation of myocardial perfusion.

We studied the use of digital angiography for the quantification of regional myocardial perfusion in the dog using selective left coronary arterial injection of radiographic contrast material as a flow dilution indicator. We developed algorithms for generating time-intensity curves from regions of interest over the proximal coronary artery and the myocardium and for densitometric error correction by subtraction of the intensity curve over a small lead blocker before logarithmic transformation. The resultant myocardial time-density curves were analyzed for time from injection to peak concentration (TPC) and for exponential washout rate (k). A linear correlation was found between absolute coronary arterial blood flow and both k (slope = 0.13, r = .85) and 1/TPC (slope = 0.18, r = .85). Reproducibility of TPC and k for repeated studies was 11% and 16%. Induced hyperemia significantly improved the sensitivity to stenosis by increasing the average difference in TPC and k between regions served by normal and stenotic coronary arteries to 65% and 80%, respectively. By combining selective coronary arterial injection with the left lateral x-ray projection it was possible to avoid most overlap of regional perfusion beds in the dog. This study suggests that contrast dilution measurements made during digital coronary angiography provide a means for assessing the hemodynamic significance of stenoses and the efficacy of therapeutic interventions.

Angiography↗

Post-reperfusion function evaluated using two-dimensional echocardiography in dog: systolic/diastolic function vs percent necrosis.

Two-dimensional echocardiography (2DE) was performed in nine dogs with three hour proximal occlusion of the left anterior descending coronary artery and seven day reperfusion for sequentially mapping systolic functions (Seg-FAC%: percent segmental fractional area change) and diastolic functions (Seg-VLAC: mean velocity of segmental luminal area change) of eight segments in a mid-papillary left ventricular short-axis cross-section. The corresponding segment functions on 2DE to the most profoundly affected segment were evaluated by triphenyl-tetrazolium-chloride staining seven days post reperfusion, and categorized in two groups in terms percent mural necrosis (N%): N% greater than or equal to 40% in group A and N% less than 40% in group B, respectively. Seg-FAC% showed a significant difference between the two groups seven days post reperfusion (13.4 +/- 9.4% in group A, 53.3 +/- 7.7% in group B), while Seg-VLAC showed significant differences in the groups at three hours post occlusion (-1.6 +/- 2.1 cm2/sec in group A and 3.2 +/- 2.6 cm2/sec in group B) and seven days post reperfusion (0.48 +/- 4.7 cm2/sec in group A and 7.5 +/- 2.4 cm2/sec in group B). At seven days post reperfusion, Seg-VLAC correlated negatively with N% (r = -0.94), while Seg-FAC% did not with N% (r = -0.58). It was concluded that Seg-VLAC, after three hours' occlusion, predicts the recovery of the regional left ventricular function seven days after reperfusion; and Seg-VLAC, seven days after reperfusion can estimate the regional transmurality of necrosis thereafter.

Animals↗

Effects of hematoporphyrin derivative and photodynamic therapy on atherosclerotic rabbits.

This study was performed to demonstrate selective uptake of hematoporphyrin derivative (HPD) within actively developing atheroma, to localize the site of uptake of HPD within the atheroma, and to determine the potential for photodynamic therapy (PDT) of atherosclerosis in the rabbit model. Fifteen rabbits were rendered atherosclerotic. Five rabbits received neither HPD nor PDT and 2 rabbits received HPD, 10 mg/kg intravenously, without subsequent irradiation. Eight other rabbits received 5 to 20 mg of HPD intravenously and subsequent intravascular 636-nm laser radiation to either the thoracic aorta or the aortic arch. A total of 32 to 288 J of laser energy was delivered through a 300-mu quartz fiber. All rabbits that received in vivo HPD had red fluorescence of their aortas when placed under ultraviolet light. The pattern of fluorescence corresponded precisely to the pattern of atheroma. In segments that received PDT, light microscopic examination revealed an accumulation of smooth muscle cells at the intimal surface. Fluorescence microscopy revealed a diminishing concentration gradient of HPD from intimal surface layers towards the media. Assessment of treated thoracic aortic segments revealed quantitative and qualitative differences compared with control segments. In the arch-treated segments, however, no changes were seen. It is concluded that HPD localizes within rabbit atheroma, can be detected by fluorescence and is deposited in a diminishing concentration gradient from lumen toward media. Irradiation with 636-nm light may induce qualitative and quantitative changes in atheroma.

Animals↗

Synchronized diastolic coronary venous retroperfusion: results of a preclinical safety and efficacy study.

The safety and efficacy of a new clinical synchronized diastolic retroperfusion mechanical pump and autoinflatable balloon catheter was studied in 10 dogs during and after 6 hours of left anterior descending coronary artery occlusion. Eight other dogs served as the untreated control group. Infarct size measured by triphenyltetrazolium chloride, and expressed as a percent of area at risk, was significantly reduced by retroperfusion treatment (19 +/- 18 versus 58 +/- 36, p less than 0.01). Morphologic examination of the coronary sinus and cardiac veins did not demonstrate evidence of damage from synchronized retroperfusion. There was also no evidence of excess myocardial edema in either the jeopardized ischemic or normally perfused zones. There was no evidence of significant red cell hemolysis or platelet destruction from the treatment. Thus, it appears that synchronized diastolic retroperfusion is a safe and effective treatment of acute myocardial ischemia in experimental animals and warrants clinical testing.

Animals↗