Biomedical subjects

A E Flynn

Publications and source records attributed to A E Flynn.

12 recordsLinked to original sources

PubMed1993

Effects of cardiac contraction and cavity pressure on myocardial blood flow.

Regional impairment of cardiac contraction uncouples force generation from left ventricular pressure (LVP) and may alter the determinants of the phasic pattern and transmural distribution of coronary flow. In anesthetized, open-chest dogs with maximal coronary vasodilation, we studied the effects of abolishing local contraction and changing cavity pressure on phasic myocardial inflow and net transmural flow in a region of left ventricular free wall. With contraction present, the normalized amplitude of distal phasic coronary velocity (NAmp) was not significantly different at normal vs. low LVP (1.00 vs. 0.92 +/- 0.09, respectively, intracoronary lidocaine, however, NAmp varied with LVP (1.62 +/- 0.25 at normal LVP, 0.85 +/- 0.22 at low LVP, P < 0.0001). With contraction present, inner-to-outer flow ratio was not consistently different at normal vs. low LVP (0.47 +/- 0.15 vs. 0.64 +/- 0.28, respectively, P = NS) but was consistently higher at low than at normal LVP with contraction absent (1.01 +/- 0.30 vs. 1.84 +/- 0.38, respectively, P < 0.0001). During uniform global function, contraction is the main determinant of phasic amplitude and transmural distribution of myocardial flow. When regional contraction is abolished, allowing passive deformation of the wall during systole, LVP assumes a powerful role.

Animals↗

PubMed1992

Does systolic subepicardial perfusion come from retrograde subendocardial flow?

To examine the influence of cardiac contraction on systolic coronary flow and transmural blood flow distribution, we measured phasic blood flow velocity in distal extramural coronary arteries by Doppler velocimeter and regional myocardial blood flow by radiolabeled microspheres while the heart was beating and during prolonged diastoles in 12 dogs. A servo-controlled coronary perfusion circuit allowed mean coronary pressure to be selected and maintained during beating and diastolic conditions. In epicardial arteries just proximal to their entrance into the myocardium, blood flow was either negligible or reverse in direction during systole. When the heart was beating, subepicardial blood flow was 24.2 +/- 12.3% higher than during asystole (5.05 +/- 0.91 and 4.11 +/- 0.79 ml.min-1.g-1 for beating and prolonged diastoles, respectively; P less than 0.01). In the subendocardium, flow was 49.8 +/- 14.7% lower in the beating condition than during prolonged diastoles (4.23 +/- 1.46 and 8.26 +/- 1.71 ml.min-1.g-1 for beating and asystole, respectively; P less than 0.01). When heart rate was increased stepwise from 60 to 150 beats/min, subendocardial flow fell approximately linearly; flow to the superficial layer was relatively unaffected. In beating hearts, lowering mean left main coronary artery (LMCA) pressure from 80 to 50 mmHg resulted in more systolic reverse flow and a fall in inner-to-outer flow ratio from 0.82 +/- 0.18 to 0.66 +/- 0.34 (P less than 0.05). Because mean LMCA pressure was held constant when the heart was stopped, differences in regional blood flow between beating and diastolic conditions were primarily due to cardiac contraction. Because little or no blood entered the myocardium from the extramural arteries during systole, we conclude that the decrease in subendocardial flow and the increase in subepicardial flow were caused by retrograde pumping of blood from the deep layer to the superficial layer of the left ventricle. Systolic retrograde flow to the subepicardium may help explain this layer's relative protection from ischemia.

Animals↗

PubMed1992

Validation of a Doppler guide wire for intravascular measurement of coronary artery flow velocity.

BACKGROUND: An improved intravascular ultrasonic Doppler device could aid the clinical assessment of coronary hemodynamics. We evaluated a new device consisting of a 12-MHz piezoelectric transducer integrated onto the tip of a 0.018-in. flexible, steerable angioplasty guide wire. METHODS AND RESULTS: Doppler spectra were recorded in model tubes with pulsatile blood flow and in-line electromagnetic flowmeter. In four straight tubes (i.d., 0.79-4.76 mm), the time average of spectral peak velocity (APV) was linearly related to blood flow (QEMF) (r2 greater than or equal to 0.98 for each tube). A Doppler-derived quantitative flow estimate (QD) was calculated as the product of vessel cross-sectional area and mean velocity, with mean velocity estimated as 0.5 x APV. The slope of QD versus QEMF for the four tubes was near unity. APV was less accurate in a 7.94-mm straight tube and in tortuous segments. In four dogs, the left circumflex coronary artery (LCx) was perfused from the femoral artery via a cannula with in-line electromagnetic flowmeter. Good-quality signals were obtained in proximal and distal LCx vessels 3.3-1.2 mm in diameter. APV varied linearly with QEMF (r2 greater than or equal to 0.99 in the cannula, r2 = 0.93-0.99 in proximal LCx, and r2 = 0.86-0.99 in distal LCx). QD was calculated by quantitative angiography to determine proximal LCx diameter. For all dogs combined, the slope of QD versus QEMF was 0.95 in the cannula and 0.85 in the proximal LCx. CONCLUSIONS: The Doppler guide wire measures phasic flow velocity patterns and linearly tracks changes in flow rate in small, straight coronary arteries. It should facilitate measurement of phasic coronary flow velocity during coronary angiography and angioplasty.

Animals↗

PubMed1992

Effect of intracoronary nitroglycerin administration on phasic pattern and transmural distribution of flow during coronary artery stenosis.

BACKGROUND: Nitroglycerin is effective in relieving myocardial ischemia; however, intracoronary nitroglycerin often fails to relieve angina and has been reported to have deleterious effects on subendocardial blood flow. To understand the mechanisms involved, we evaluated the direct effect of nitroglycerin on coronary circulation of the ischemic hearts. METHODS AND RESULTS: We measured the phasic pattern of intramyocardial coronary arterial flow with an 80-channel, 20-MHz pulsed Doppler ultrasound flowmeter under moderate to severe coronary artery stenosis (distal perfusion pressure approximately 45 mm Hg group 1, n = 6) and transmyocardial blood flow distribution using radioactive microspheres while maintaining coronary pressure at a low constant level (40 mm Hg, group 2, n = 6). In anesthetized open-chest dogs, the left main coronary artery was perfused directly from the right carotid or femoral artery. In this bypass circuit, pressure was controlled with an occluder or a reservoir was connected to the circuit. In group 1, the systolic and diastolic pressures distal to the stenosis decreased significantly after intracoronary administration of nitroglycerin at maximal coronary flow from 66.5 +/- 18.5 to 56.5 +/- 13.8 mm Hg (p less than 0.01) and from 36.6 +/- 14.4 to 27.5 +/- 8.9 mm Hg (p less than 0.01), respectively. The phasic pattern of the septal artery flow was predominantly diastolic and was characterized by systolic reverse flow even in the absence of stenosis. Coronary stenosis increased systolic reverse flow. Nitroglycerin increased diastolic forward flow (p less than 0.05) but augmented systolic reverse flow markedly (p less than 0.001). In group 2, nitroglycerin increased subepicardial flow (p less than 0.05) but failed to increase subendocardial flow. With the administration of nitroglycerin, the subendocardial-to-subepicardial flow ratio decreased significantly from 0.73 +/- 0.19 to 0.32 +/- 0.14 (p less than 0.01). CONCLUSIONS: The increased systolic reverse flow after intracoronary administration of nitroglycerin may be closely related to failure of subendocardial blood flow to increase with increase subepicardial flow.

Animals↗

PubMed1991

Cardiac contraction affects deep myocardial vessels predominantly.

To evaluate the roles of intramyocardial forces and systolic ventricular pressure in myocardial flow in the different layers separately, we measured myocardial flow in rabbit hearts during stable systolic contracture with left ventricular pressures of 60 (n = 5) and 0 mmHg (n = 5) and during stable diastolic arrest (n = 5). We also measured the number and size of the intramyocardial vessels after perfusion fixation (systolic arrest, n = 5; diastolic arrest, n = 5). In 25 rabbits, hearts were excised and perfused from the aortic root. Systolic arrest was achieved by perfusion of a low-Ca2+ Tyrode solution containing 2.0 mM Ba2+. Diastolic arrest was achieved by intraventricular injection of 700-1,000 mg pentobarbital sodium and was maintained by perfusion with St. Thomas cardioplegic solution. At perfusion pressure of 100 mmHg, subendocardial flow was lower than subepicardial flow during systolic arrest regardless of left ventricular pressure, whereas during diastolic arrest, subendocardial flow was higher than subepicardial flow. Subendocardial-to-subepicardial flow ratios for a physiological range of perfusion pressures were lower during systolic arrest with low rather than with high left ventricular pressure. Small arteriolar and capillary densities showed no difference between subendocardium and subepicardium. During systolic arrest, diameters of subendocardial terminal arterioles (4.6 +/- 1.3 microns) and capillaries (4.0 +/- 1.3 microns) were smaller than those in the subepicardium (8.8 +/- 1.7 and 7.1 +/- 1.6 microns, respectively; P less than 0.0001), whereas during diastolic arrest, diameters of subendocardial terminal arterioles (10.1 +/- 2.0 microns) and capillaries (7.6 +/- 1.8 microns) were slightly larger than those in the subepicardium (9.5 +/- 1.5 and 6.7 +/- 1.0 microns, respectively; P less than 0.01). We conclude that cardiac contraction predominantly affects subendocardial vessels and impedes subendocardial flow more than subepicardial flow regardless of left ventricular pressure.

Animals↗

PubMed1990

Nonuniform blood flow in the canine left ventricle.

In order to investigate the relationship between coronary perfusion pressure and blood flow distribution in the left ventricle (LV), we measured myocardial blood flow in small regions using radioactive microspheres in six anesthetized, open-chest dogs. Mean coronary perfusion pressure (CPP) was controlled with a femoral artery to left main coronary artery shunt which included a pressurized, servo-controlled blood reservoir. In each dog, we measured flow in 192 regions of the LV free wall (mean weight per region = 206 +/- 38 mg) at different perfusion pressures. At CPP = 80 mm Hg, blood flow to individual regions varied fourfold (0.30 to 1.18 ml/min/g; relative dispersion (RD) = 21.8 +/- 2.3%). At CPP = 50 mm Hg, flow varied over sevenfold (0.08 to 0.60 ml/min/g; RD = 42.8 +/- 10%; P less than 0.01 vs 80 mm Hg). This relationship between flow variability and CPP was present within individual LV layers as well between layers and is much higher than the error associated with the microsphere technique. We conclude that blood flow to small regions of the LV is markedly nonuniform. This heterogeneity becomes more profound at lower CPP. These findings suggest that (1) global measurements of coronary flow must be interpreted with caution, and (2) even in hearts with normal coronary arteries some regions of the LV are more susceptible to ischemia than others. In addition, these findings may help explain the patchy nature of myocardial damage that occurs following periods of low coronary pressure or inadequate myocardial protection during cardiopulmonary bypass.

Animals↗

PubMed1990

Nonuniform loss of regional flow reserve during myocardial ischemia in dogs.

To determine whether coronary vasodilator reserve that persists during myocardial ischemia is present in all left ventricular regions, we measured regional blood flow in 192 left ventricular pieces (mean weight, 201 mg) in each of eight dogs by using radioactive microspheres while perfusing the left main coronary artery at 70, 50, 40, and 30 mm Hg. Flows were measured before and during adenosine infusion to determine flow reserve. Perfusion at 40 and 30 mm Hg produced ischemia in all dogs. At 70 mm Hg, 100% of left ventricular regions had significant flow reserve, compared with 92%, 55%, and 8% during perfusion at 50, 40, and 30 mm Hg, respectively. A greater amount of flow reserve and a greater number of regions responded to adenosine in the subepicardium than in the subendocardium at 50, 40, and 30 mm Hg. We conclude that coronary flow reserve persists in only a subset of left ventricular regions during ischemia and that the number of regions with persistent flow reserve decreases with perfusion pressure. These findings may best be explained by a model in which regional ischemia is a maximal coronary vasodilator and persistent pharmacological vasodilator reserve seen when global markers indicate ischemia simply reflects persistent endogenous flow reserve in myocardial regions not yet ischemic.

Adenosine↗

PubMed1990

Profound spatial heterogeneity of coronary reserve. Discordance between patterns of resting and maximal myocardial blood flow.

We examined the ability of individual regions of the canine left ventricle to increase blood flow relative to baseline rates of perfusion. Regional coronary flow was measured by injecting radioactive microspheres over 90 seconds in seven anesthetized mongrel dogs. Preliminary experiments demonstrated a correlation between the regional distributions of blood flow during asphyxia and pharmacological vasodilatation with adenosine (mean r = 0.75; 192 regions in each of two dogs), both of which resulted in increased coronary flow. Subsequent experiments, during which coronary perfusion pressure was held constant at 80 mm Hg, examined the pattern of blood flow in 384 regions (mean weight, 106 mg) of the left ventricular free wall during resting flow and during maximal coronary flow effected by intracoronary adenosine infusion. We found that resting and maximal flow patterns were completely uncorrelated to each other in a given dog (mean r = 0.06, p = NS; n = 3 dogs). Furthermore, regional coronary reserve, defined as the ratio of maximal to resting flow, ranged from 1.75 (i.e., resting flow was 57% of maximum) to 21.9 (resting flow was 4.5% of maximum). Thus, coronary reserve is spatially heterogeneous and determined by two distinct perfusion patterns: the resting (control) pattern and the maximal perfusion pattern. Normal hearts, therefore, contain small regions that may be relatively more vulnerable to ischemia. This may explain the patchy nature of infarction with hypoxia and at reduced perfusion pressures as well as the difficulty of using global parameters to predict regional ischemia. Despite the wide dispersion of coronary reserve, we found, by autocorrelation analysis, that reserve in neighboring regions (even when separated by a distance of several tissue samples) was significantly correlated. This also applied to patterns of resting myocardial flow. Thus, both resting coronary blood flow and reserve appear to be locally continuous and may define functional zones of vascular control and vulnerability, respectively.

Adenosine↗

PubMed1990

Heterogeneous delivery of cardioplegic solution in the absence of coronary artery disease.

The prevention of intraoperative myocardial damage with cardioplegic solution depends in large measure on the completeness of its delivery. We created a model to study the regional flow distribution of cardioplegic solutions in nondiseased, diastolically arrested, maximally vasodilated canine hearts. Global and regional myocardial flows were measured at different perfusion pressures in hearts perfused either with blood cardioplegic solution (n = 8) or oxygenated crystalloid cardioplegic solution (n = 2). As coronary perfusion decreased, flow in all layers fell significantly (p less than 0.001). This fall was most dramatic in the subendocardium (p less than 0.05). With both types of cardioplegic solutions, the relationship between pressure and flow was nonlinear: At low coronary perfusion pressures, a given change in pressure resulted in a smaller change in flow than at higher perfusion pressures. In addition, we found that in all dogs and at all pressures there was profound variability in the delivery of cardioplegic solution to different small regions of the left ventricular free wall. At a perfusion pressure of 40 mm Hg, the extremes of regional flow differed on average by 203%. This heterogeneity increased significantly with decreasing perfusion pressures. At the lowest perfusion pressure measured (20 mm Hg), the extremes of regional flow differed on average by 365%. These findings emphasize the importance of coronary pressure on the delivery of cardioplegic solution. At low perfusion pressures, not only is mean flow reduced, but a greater number of regions receive limited amounts of cardioplegic solution. These observations may explain the patchy nature of subendocardial damage seen with inadequate myocardial protection.

Animals↗

PubMed1989

Esophageal perforation.

Sixty-nine patients with perforation of the esophagus were treated at the University of California, San Francisco, from 1977 to 1988. The perforation was iatrogenic in 33 (48%) of the patients, spontaneous in 8 (12%), and a result of external trauma in 23 (33%). Clinical findings included chest pain in 36 (52%) of 69 patients, subcutaneous emphysema in 22 (32%) of 59 patients, and pneumomediastinum in 21 (36%) of 59 patients. Esophagograms demonstrated the perforation in 40 (93%) of 43 patients. Treatment delays of more than 24 hours occurred in about half of spontaneous and iatrogenic perforations, but when the perforation was due to external trauma, treatment was delayed infrequently. Operative therapy in 59 (86%) of the patients included primary closure in 44 patients, drainage alone in 9 patients, and Celestin tube placement in 1 patient. Four patients with benign strictures had esophagectomy, and 4 patients with achalasia had Heller myotomy in addition to closure of the perforation. Eight (12%) of the patients were treated nonoperatively. For thoracic perforations, nonoperative treatment was reserved for patients who were diagnosed late but who had minimal evidence of sepsis. Seven (10%) of the patients died. Factors that influenced outcome included cause of perforation, anatomic location, and patient age. Our study shows that a high index of suspicion, aggressive use of esophagography, and individualized treatment are necessary for the best results when treating esophageal perforation.

Adolescent↗

PubMed1989

Acute tracheobronchial injury.

We reviewed our experience with tracheal and bronchial trauma from 1977 to 1988. There were 22 patients with tracheobronchial injuries treated in this period. Seventeen (77%) of the injuries were due to penetrating trauma and five (23%) were due to blunt trauma. Thirteen patients had major associated injuries, including six esophageal injuries. The most common physical findings were tachypnea (13 patients) and subcutaneous emphysema (nine patients). Eight patients presented with airway obstruction. All patients with penetrating cervical tracheal injuries underwent neck exploration and primary repair. All blunt injuries were diagnosed by bronchoscopy. Three patients with blunt injuries were treated with primary repair. Two patients with blunt chest trauma and small bronchial tears were treated nonoperatively with good results. All three deaths (14% mortality rate) were due to associated injuries. We conclude that patients with penetrating tracheobronchial injuries should be managed by surgical exploration and primary repair, although selected patients with blunt injury may be treated nonoperatively.

Adult↗

PubMed1989

Quantitating error in blood flow measurements with radioactive microspheres.

Accurate determination of the reproducibility of measurements using the microsphere technique is important in assessing differences in blood flow to different organs or regions within organs, as well as changes in perfusion under various experimental conditions. The sources of error of the technique are briefly reviewed. In addition, we derived a method for combining quantifiable sources of error into a single estimate that was evaluated experimentally by simultaneously injecting eight or nine sets of microspheres (each with a different radionuclide label) into four anesthetized dogs. Each nuclide was used to calculate blood flow in 145-190 myocardial regions. We compared each flow determination (using a single nuclide label) with a weighted mean for the piece (based on the remaining nuclides). The difference was defined as "measured" error. In all, there were a total of 5,975 flow observations. We compared measured error with theoretical estimates based on the Poisson error of radioactive disintegration and microsphere entrapment, nuclide separation error, and reference flow error. We found that combined estimates based on these sources completely accounted for measured error in the relative distribution of microspheres. In addition, our estimates of the error in measuring absolute flows (which were established using microsphere reference samples) slightly, but significantly, underestimated measured error in absolute flow.

Animals↗