Blood pressure responses of wild giraffes studied by radio telemetry.

Blood pressure was telemetered from transducers chronically implanted in the carotid arteries of two adult, wild, male giraffes captured and released near Kiboko, Kenya. Cerebral perfusion pressure ranged from 280/180 mm-Hg while the animal was lying with its head on the ground to 125/75 mm-Hg when it was standing erect; it varied between these levels during spontaneous activity such as walking, grazing, and running.

Detection of latent coronary stenosis in conscious dogs: regional functional and electrocardiographic responses to isoprenaline.

A conscious animal model was developed in which coronary stenosis could be produced while regional myocardial function and local surface electrocardiograms were measured. Responses to isoprenaline stress in the presence of mild (latent) coronary stenosis were then examined. In the absence of coronary stenosis, isoprenaline produced increases in regional function and no change in the surface VCG; at higher doses, increases in the endocardial ST segments occurred. After partial coronary stenosis, which produced no apparent regional dysfunction or electrocardiographic changes, isoprenaline infusion for 3 min (0.02 microgram . kg-1 . min-1) rapidly produced decreases in percentage wall thickening (average 17 +/- 4%, mean +/- SE, P < 0.01) and increases in the mean sum of VCG ST segments by 0.23 +/- 0.06 mV (P < 0.05). 1 min after stopping isoprenaline, most dogs showed further significant deterioration of both measures of ischaemia, but by 5 min there was no significant mean change from control. We conclude that in the presence of latent partial coronary stenosis, stress due to mild sympathomimetic stimulation alone can rapidly induce regional myocardial ischaemia. Deterioration of regional myocardial contractile function during such stress can provide as sensitive means of detecting latent coronary obstruction.

Coronary arterial reperfusion. III. Early and late effects on regional myocardial function and dimensions in conscious dogs.

Regional myocardial function was studied in five conscious chronically instrumented dogs for 4 weeks after coronary reperfusion following a 2 hour period of occlusion of the left circumflex coronary artery. A cuff and flowmeter were placed around the left circumflex coronary artery, and a micromanometer and three pairs of ultrasonic crystals were implanted 1 cm apart subendocardially in control, marginal and ischemic segments of the left ventricle. Control normal segments showed progressive increases in end-diastolic length and extent of active shortening. Ischemic segments tended to show slight improvement early after reperfusion, but in succeeding weeks, despite some improvement in shortening, they showed progressive decreases in end-diastolic length compatible with subendocardial tissue loss. In marginally ischemic segments, shortening initially remained depressed after reperfusion, but showed late recovery so that shortening and end-diastolic length were not different from control values by 4 weeks. These results contrasted with findings in five similarly studied dogs subjected to permanent coronary occlusion; in that group the data suggested greater tissue loss and less recovery of function in marginal and ischemic segments. The late return of segmental function and reduced loss of subendocardial tissue several weeks after coronary reperfusion suggest that substantial time periods may be required to assess the ultimate effect of therapeutic interventions. The findings further indicate that in this experimental model the usual time constraints for occurrence of irreversible tissue damage do not apply to all of the myocardium within the ischemic zone.

Dynamic changes in left ventricular wall thickness and their use in analyzing cardiac function in the conscious dog.

The thickness of the left ventricular free wall and internal chamber diameter were continuously measured by pairs of ultrasonic crystals together with left ventricular pressure in normal conscious dogs. During the resting state, wall thickness decreased abruptly with the onset of atrial contraction from 10.5 mm to an average end-diastolic valueof9.8 mm. In contrast to most previous studies, there was no change in wall thickness during isovolumic systole, and with ejection the wall thickened by 31.3 percent of end-diastolic wall thickness. Atrial pacing, phenylephrine, isoproterenol and propranolol produced significant changes in chamber size with reciprocal changes in wall thickness. In addition, changes in the extent and velocity of left ventricular chamber shortening in the minor equator were associated with comparable reciprocal changes in the extent and velocity of free wall thickening (correlation coefficients 0.97 to 0.99). During acute coronary occlusion, progressive reductions in the extent and velocity of regional wall shortening with partial ischemia were associated with comparable changes in systolic wall thickening characteristics (r = 0.96 and 0.95), and holosystolic elongation in fully ischemic areas was associated with holosystolic wall thinning. During chronic pressure overload, despite wall thickening, the relation between chamber shortening and wall thickening were retained and direct computation of dynamic wall stress variations was possible. These measurements allowed precise definition of the dynamics of the left ventricular wall during normal and abnormal cardiac states. The demonstration that in the absence of regional dysfunction analysis of wall thickness in a single region of ventricular free wall can be used to describe myocardial and overall left ventricular function, as well as regional function in the presence of ischemia, constitutes a new approach to the assessment of cardiac function that has potential for echocardiographic applications.

End-systolic dimension-wall thickness relations during myocardial ischemia in conscious dogs. A new approach for defining regional function.

Overall and regional left ventricular (LV) function was studied during progressive coronary stenosis in conscious dogs by determining the relations at end-systole between LV pressure, chamber dimensions, and regional LV wall thickness. An index of regional wall stress was also analyzed. Using ultrasonic dimension gauges, measurements were made of LV wall thickness in control and ischemic regions, and the external long- and short-axis LV diameters were determined; an implanted micromanometer measured LV pressure. Internal LV diameters were obtained from the external diameters by subtraction of wall thickness, and the index of regional wall stress employed a thick-walled ellipsoidal model. During regional ischemia, the LV long axis at end-systole did not change, whereas the short-axis diameter progressively increased (from 24 +/- 7 mm [standard deviation] to 30 +/- 9 mm, p less than 0.001, indicating a more spherical LV shape during ischemia). The end-systolic pressure did not change, and therefore the end-systolic pressure-diameter relation shifted progressively, suggesting a global decrease in LV contactility. The end-systolic points relating LV wall thickness in the ischemic region to the end-systolic LV pressure revealed the regional nature of the abnormality, showing a progressive displacement to the left, whereas there was no significant displacement of this relation in the control region. The application of this index over a range of loading conditions during partial vena caval occlusion was illustrated. Thus, the regional end-systolic wall thickness-pressure relation provides a new index for defining the regional contractile state of the LV myocardium which is potentially load-independent and offers the possibility for echocardiographic application.

Left ventricular geometry during partial and complete coronary occlusion in the conscious dog.

Seven dogs were instrumented with a left ventricular micromanometer and pairs of ultrasonic crystals to measure left ventricular wall thicknesses (control and ischemic regions) and short and long left ventricular axes; cuff occluders were placed around the left circumflex coronary artery and the inferior vena cava. Measurements were performed at rest, after 2 min of partial and complete coronary occlusion, and 1 and 10 min after release of partial and complete coronary occlusion. Left ventricular wall thickness in the ischemic region showed reduced systolic thickening during partial coronary occlusion and systolic thinning during complete coronary occlusion. During diastole, at zero pressure (inferior vena cava obstruction) the left ventricular short axis was unchanged during partial coronary occlusion but significantly increased (creep) during complete coronary occlusion (P less than 0.05), whereas after release of both partial and complete coronary occlusion the short axis at zero pressure decreased significantly (P less than 0.025). Left ventricular wall thickness at zero diastolic pressure in the ischemic region was significantly thinner during complete coronary occlusion than during control and significantly thicker (reactive hyperemia) 1 min after release of both partial and complete coronary occlusion. The long left ventricular axis remained unchanged during the entire experiment. At end-diastole, the long/short axis ratio was normal during partial (1.72; control 1.68; NS) and complete coronary occlusion (1.69; NS), but it decreased significantly from control of 2.10 to 1.99 with partial coronary occlusion and 1.85 with complete coronary occlusion (P less than 0.01). The changes in the L/S ratio during partial and complete coronary occlusion were proportional to changes in left ventricular chamber volume (correlation coefficient 0.94). Our data show that left ventricular shape remains normal at end-diastole during partial and complete coronary occlusion but becomes significantly more spherical at end-systole, with reduction of the normal tendency for the ventricle to become more elliptical during systole. These elliptical and spherical shape changes of the left ventricle during partial and complete coronary occlusion appear to be closely related to the chamber volume.

Regional Myocardial function in the conscious dog during acute coronary occlusion and responses to morphine, propranolol, nitroglycerin, and lidocaine.

Regional myocardial function following occlusions of the circumflex coronary artery was studied in unanesthetized dogs using minature ultrasonic crystal pairs implanted subendocardially within the left ventricle for measurement of control, marginal, and ischemic lengths. As early as five beats after coronary occlusion, reduced function was apparent in ischemic zones, and an increase in heart rate occurred (78 to 115 beats/min) at an average of 25 sec. In the control zones, shortening initially increased from a constant end-diastolic length, but later end-diastolic length also increased by 7.5%. Shortening in the marginal zones was reduced by 50% at 90 sec as holosystolic expansion developed in the ischemic zones. On reperfusion, systolic function returned to normal within a few minutes while protodiastolic abnormalities persisted for up to 45 min. With coronary occlusions longer than two minutes most dogs exhibited arousal and further tachycardia; this reaction was prevented by morphine. During two minute occlusions morphine also decreased the heart rate increase by 37%, and marginal segment shortening was improved by 40%. Prior administration of propranolol also decreased heart rate during coronary occlusion and produced similar improvement in marginal segment function; however, in contrast to morphine, there was depression of contraction in the control segments. Nitroglycerin given during coronary occlusion caused decreases in end-diastolic length of all segments and increased shortening in the marginal segment by 28%. Lidocaine administered during coronary occlusion produced a mild depression of myocardial function in all regions of the heart.

Nonuniformity of inner and outer systolic wall thickening in conscious dogs.

Transmural differences in systolic wall thickening were analyzed in 13 conscious dogs by implanting sonomicrometers to continuously measure total wall thickness (WT) and outer WT approximately half the distance through the myocardium at a closely adjacent location. Inner WT was derived by subtraction of outer WT from total WT. Outer wall measurements spanned, on average, the outer 44 +/- 10% (+/- SD) of the wall; derived inner wall measurements spanned the remaining 56 +/- 10%. At rest the fractional contribution (FC) of the outer wall to total systolic wall thickening was 29 +/- 9%, which was significantly less than the FC of the inner wall, 71 +/- 9%. These data are in good agreement with simplified modeling of a cross section of the left ventricle as two concentric rings that predicts that the FC of inner and outer halves of the wall should be approximately 67 and 33%, respectively. During treadmill exercise, the extent of both inner and outer thickening increased significantly (30 and 29%, respectively) but the relative FC of the inner and outer wall remained the same. The data indicate that systolic wall thickening is nonuniform and that this nonuniformity remains constant during the increased inotropic and chronotropic stimulation associated with exercise.

Effect of the combination of diltiazem and atenolol on exercise-induced regional myocardial ischemia in conscious dogs.

The effect of combination therapy with diltiazem and atenolol on the regional myocardial blood flow-function relationship was studied in eight conscious dogs with chronic coronary artery stenosis. An ameroid constrictor and hydraulic occluder were placed around the left circumflex coronary artery, sonomicrometers were implanted for measuring wall thickness in control and ischemic regions, and regional myocardial blood flow was measured with the microsphere method. Eighteen days (average) after surgery, resting regional myocardial function and blood flow were normal, but treadmill exercise induced severe regional myocardial dysfunction in the posterior wall (wall thickening during systole reduced from 25.5% to 2.7%, a 90% reduction). Subendocardial blood flow decreased by 68% from the control standing value, while subepicardial flow increased. An identical exercise bout was performed 3 hr after administration of atenolol (1.0 mg/kg orally) and 15 min after administration of diltiazem (0.3 mg/kg iv). Heart rate during running was significantly lower as were left ventricular peak systolic pressure, end-diastolic pressure, and peak dP/dt. Wall thickening in the control region was not augmented during exercise after atenolol and diltiazem. There was less dysfunction in the ischemic region (35% reduction) and the improved performance was accompanied by a substantial increase in subendocardial perfusion (0.31 +/- 0.14 vs 0.61 +/- 0.30 ml/min/g, a 36% reduction from rest). Epicardial flow was unchanged, and the endocardial/epicardial ratio increased (0.27 +/- 0.13 vs 0.62 +/- 0.29). Recovery time for regional wall thickening also improved. The beneficial effects of the combination of atenolol and diltiazem in a preparation of single-vessel chronic coronary stenosis were shown to be significantly greater than those of either drug alone.

Cyclical coronary flow reductions in conscious dogs equipped with ameroid constrictors to produce severe coronary narrowing.

In conscious dogs equipped with ameroid constrictors to produce gradual coronary occlusion, coronary flow velocity was monitored prior to complete occlusion when coronary constriction was severe (resting flow velocity reduced by 10-50% from control recordings made days after ameroid implantation). In six of the ten dogs, we observed spontaneous cyclical variations in coronary flow velocity, characterized by gradual reduction in flow followed by very abrupt restoration of flow. The cyclic coronary flow reductions were observed between 20 and 31 days after ameroid implantation. These changes in flow bear striking similarity to those observed by previous investigators using anesthetized, open-chest canine preparations, in which the role of platelets was clearly demonstrated. Consequently, we hypothesize that spontaneous platelet aggregation and de-aggregation within the severely narrowed coronary lumen (enclosed by the ameroid constrictors) could account for our observations.

Sustained regional dysfunction produced by prolonged coronary stenosis: gradual recovery after reperfusion.

Prolonged nontransmural ischemia was produced and the early and late effects of reperfusion were studied in 10 conscious dogs instrumented over the long term. Five hours of partial circumflex coronary artery stenosis was produced with a hydraulic occluder, followed by gradual release over 20 min, with measurements of left ventricular pressure, regional myocardial function (systolic wall thickening by sonomicrometry), coronary blood flow velocity (pulsed Doppler), and myocardial blood flow (microspheres). During coronary stenosis the occluder was adjusted frequently to maintain a reduction of systolic wall thickening to 50% to 75% of control (average 62.6% of control). Myocardial blood flow in the ischemic area at 4 hr of partial coronary stenosis was reduced in the inner layers of the myocardium (subendocardium, from 0.81 +/- 0.18 at control to 0.36 +/- 0.08 SD, p less than .01; midwall, from 0.77 +/- 0.20 to 0.46 +/- 0.07 ml/min/g, p less than .01), accompanied by significant ST segment elevation on the subendocardial electrogram (0.83 +/- 0.96 to 4.58 +/- 4.10 mV; p less than .05) and decreased left ventricular dP/dt (3503 +/- 462 to 2991 +/- 339 mm Hg/sec; p less than .01). Within a few minutes after complete release of partial coronary stenosis, ST segments returned to control and myocardial blood flow of the inner layers was increased (subendocardium, 1.37 +/- 0.39, p less than .01; midwall, 0.97 +/- 0.28, p less than .05), but systolic wall thickening and left ventricular dP/dt were significantly depressed and remained reduced at 24, 48, and 72 hr when myocardial blood flow was normal. By seven days, systolic wall thickening and left ventricular dP/dt had returned to control (94.1 +/- 7.0% of control, 3353 +/- 605 mm Hg/sec, respectively; NS). Histologic changes caused by ischemia constituted only 2.7% (average) of the tissue between the crystals in the ischemic wall, but ischemic damage in the posterior papillary muscle, which did not contain crystals, was 31.9%. Thus, regional myocardial dysfunction reduced by nontransmural ischemia for 5 hr persisted for at least 3 days, with only slight damage to the left ventricular free wall but considerable infarction of the posterior papillary muscle. Full recovery of regional and global contractile function of the free wall then occurred within a period of 1 week.

Effect of exercise on the relationship between myocardial blood flow and systolic wall thickening in dogs with acute coronary stenosis.

Relationships between regional myocardial perfusion and transmural function, both during treadmill exercise and at rest, were examined in conscious dogs with varying degrees of coronary stenosis produced by a hydraulic occluder. In 13 dogs we measured myocardial blood flow with microspheres (10-12 microns in diameter) and regional systolic wall thickening (%). During exercise with coronary stenosis, myocardial blood flow was characterized by nonuniform distribution, and associated with regional dysfunction. The relationships between normalized myocardial blood flow and normalized %wall thickening during exercise with coronary stenosis were linear, with significantly different slopes (mean myocardial blood flow: y = 1.23x - 0.16, r = 0.93; subendocardial myocardial blood flow: y = 1.50x - 0.02, r = 0.86; subepicardial myocardial blood flow: y = 0.83x - 0.18, r = 0.87). To fill the gap between available subendocardial and subepicardial data during exercise with coronary stenosis and control points, however, would require nonlinear components. In 10 of the dogs, coronary stenosis at rest was also produced to compare regional myocardial blood flow - %wall thickening relations at rest with those during steady state exercise. The absolute mean myocardial blood flow - %wall thickening relation during exercise with coronary stenosis (y = 11.6x - 1.9, r = 0.90) was significantly shifted rightward from the resting relation (y = 25.3x -2.1, r = 0.80). However, when changes in %wall thickening were plotted vs. myocardial blood flow per beat, the relationships at rest and exercise were nearly superimposable. Likewise, relations between normalized myocardial blood flow and changes in %wall thickening at rest and exercise were not significantly different. We conclude: %wall thickening during exercise is directly related to changes in mean myocardial blood flow but is related in nonlinear fashion to changes in subepicardial and subendocardial myocardial blood flow; %wall thickening may provide a reliable index of the relative transmural flow distribution during exercise as well as at rest; during brief bouts (5-8 minutes) of exercise with coronary stenosis, the relationship between stabilized regional contractile dysfunction and level of myocardial blood flow per beat is the same as that during coronary stenosis at rest.

Isoproterenol-induced myocardial dysfunction in dogs with coronary stenosis.

Stress-induced regional myocardial ischemia in the presence of mild coronary stenosis was studied in five dogs 2-4 wk after implantation of pairs of ultrasonic crystals to measure left ventricular wall thickening (% delta WT) and subendocardial segmental shortening (% delta L). Isoproterenol (0.2 micrograms.kg-1.min-1) was infused before and after production of coronary stenosis, which produced no resting dysfunction. During isoproterenol infusion with coronary stenosis % delta WT and subendocardial % delta L were significantly decreased although blood flow was comparable to conditions at rest, indicating that the demand for blood flow exceeded supply. Linear regression analysis of mean transmural blood flow versus % delta WT during isoproterenol demonstrated that wall thickening was significantly related to changes in mean blood flow: y (percentage wall thickening) = 27.5 X (transmural blood flow) -8.2 (r = 0.83); likewise % delta L was significantly related to subendocardial blood flow during isoproterenol infusion: y (percentage shortening) = 17.1 X (subendocardial blood flow) -0.4 (r = 0.85). These results indicate that both regional % delta WT and % delta L sensitively reflect the adequacy of myocardial perfusion even during stress-induced changes in myocardial O2 demands and blood flow.

Comparison of postpacing and exercise-induced myocardial dysfunction during collateral development in conscious dogs.

In 10 conscious dogs, a model was developed for studying regional contractile responses in a coronary collateral-dependent bed. Regional myocardial function was compared after terminating a maximum paced rate of 240 beats/min maintained for 3 minutes (postpacing period) with that during telemetry-monitored exercise at comparable heart rates (average 252 +/- 34 beats/min, duration 2.4 minutes) at different times during collateral development. Ultrasonic dimension gauges were used to measure control and ischemic segment (CS and IS) lengths and ischemic zone regional wall thickness (IW). An ameroid constrictor and a Doppler flow probe were placed around the left circumflex coronary artery, and pacing electrodes were sutured to the right ventricle. An average of 23 days postoperatively, coronary obstruction was complete. Studies at that time showed that percent shortening (% delta L) of IS and percent wall thickening (% delta W) of IW decreased after pacing to 57% and 35% of control, respectively, and during exercise to 37% of control. One week later (average 30 days postoperatively), significant depression of regional function no longer occurred postpacing. However, exercise at a comparable heart rate still provoked regional dysfunction in the collateral-dependent zone: Both IS% delta L and IW% delta W decreased to 51% of control. Regional function at rest did not differ during these studies. Thus, the effectiveness of the postpacing response for detecting limited collateral reserve was eliminated by further collateral development, but regional myocardial dysfunction during exercise stress served to detect ischemia despite increased collateral circulation.

Myocardial blood flow and function with critical coronary stenosis in exercising dogs.

Critical stenosis of coronary arteries does not alter myocardial blood flow (MBF) at rest, but eliminates hyperemia and corresponds to a degree of arterial narrowing that expends subendocardial vasodilator reserve. Because subepicardial vasodilator reserve remains with critical stenosis at rest, we tested the significance of this reserve in six exercising dogs chronically instrumented to measure MBF (microspheres), regional function (systolic wall thickening with sonomicrometers), and coronary blood flow velocity (CBFV, pulsed Doppler). Critical stenosis produced with a hydraulic occluder limited CBFV and mean MBF to the resting level during treadmill exercise, but MBF was maldistributed. Subendocardial MBF decreased 50% (P less than 0.05) and subepicardial MBF increased 104% (P less than 0.01) compared with resting control conditions, suggesting that a transmural "steal" phenomenon had occurred, with augmented MBF in the subepicardial region at the expense of subendocardial MBF. Systolic wall thickening decreased markedly from 31.5 +/- 6.8 to 9.4 +/- 2.0% (P less than 0.01) during exercise, indicating that use of subepicardial vasodilator reserve with critical stenosis had little sustaining effect on regional contractile performance. Rather, subepicardial vasodilator reserve is potentially deleterious, inasmuch as a steal effect could contribute to reduced subendocardial perfusion, the primary determinant of systolic wall thickening.

Regional left ventricular wall thickness early and late after coronary occlusion in the conscious dog.

Regional wall thickness and endocardial segment lengths in normal and ischemic zones of the left ventricle were measured simultaneously with ultrasonic-dimension gauges before and after chronic circumflex artery occlusion in conscious dogs. After 3 wk, end-diastolic segment lengths (EDL) in normal zones increase 10% (P less than 0.01), shortening increased 22% (P less than 0.05), and end-diastolic wall thickness (EDWT) was reduced by 12.8% (P less than 0.01). In ischemic zones at 3 wk, EDL was reduced by 15.4% (P less than 0.01), and subendocardial shortening recovered slightly to 15% of control; EDWT increased 11% at 3 days postocclusion and thereafter remained near control values (change not significant), but systolic wall thickening improved substantially, reaching 38% of control at 3 wk. Thus, tissue loss and slight return of function occurred in the ischemic subendocardium, whereas overall wall function (as reflected by regional wall thickening) improved considerably over time. These findings suggest that recovery of function in the outer layers of the wall after myocardial infarction modifies the close correlation between regional subendocardial segment and wall thickening dynamics observed acutely.

Functional evaluation of coronary collateral development in conscious dogs.

Gradual coronary constriction was elicited in conscious dogs by means of an implanted ameroid coronary constrictor. The functional state of the coronary collateral circulation was serially evaluated by means of regional contractile responses, using brief occlusions of the left circumflex coronary artery and strenuous running in the field. Although resting regional myocardial function was unchanged throughout the study, regional myocardial shortening during coronary occlusion decreased to 9% of control at 3-4 days after the operation; it then recovered progressively to 24% at 7-9 days, 45% at 15-18 days, and 94% at 20-24 days. Concomitantly, reactive hyperemia measured with a flowmeter declined from 300% at 3-4 days to 228, 88, and 0% at 7-9, 15-18, and 20-24 days, respectively. A bout of running held 21 days after the ameroid implant when resting regional function was well maintained induced severe regional and global dysfunction. These findings indicate the usefulness of regional myocardial contractile responses in assessing coronary collateral reserve.

Effects of beta-blockade on regional myocardial flow and function during exercise.

We examined the effects of a cardioselective beta-blocking drug on exercise-induced regional myocardial ischemia in 10 conscious dogs with chronic coronary artery stenosis. An ameroid constrictor, Doppler flowprobe, and hydraulic cuff were placed around the left circumflex coronary artery, and left ventricular pressure (LVP), systolic wall thickening (% delta WT; by sonomicrometry), and myocardial blood flow (MBF; microspheres) were measured during control standing, control treadmill exercise, and identical exercise after atenolol (1 mg/kg po). Prior to study, in every dog % delta WT and MBF in the ischemic area were normal at rest, indicating collateral development. During control exercise, % delta WT in the ischemic region markedly decreased from 27 to 4%, and transmural ischemia was evident in that region. Heart rate, systolic LVP, and LV (+)dP/dt were significantly lower during exercise after atenolol than during control exercise. % delta WT in the normal area was only 81% of that during control exercise, but dysfunction in the ischemic area was improved (77% increase compared with control exercise). Accompanying the improved function was a significant increase of MBF/beat and relative MBF in the ischemic zone; the endocardial-to-epicardial ratio increased from 0.27 to 0.47. Thus atenolol improved regional MBF distribution, thereby diminishing exercise-induced regional myocardial dysfunction and accelerating its recovery.

Regional myocardial perfusion and wall thickening during ischemia in conscious dogs.

We examined in conscious dogs the effects of reductions in myocardial blood flow (MBF) in three different layers across the wall on regional myocardial contractile function in the ischemic zone, measured as systolic wall thickening (%WT). In 16 dogs, %WT was measured with sonomicrometry and MBF was determined with microspheres (10- to 12-microns diam) during coronary stenosis of the left circumflex coronary artery. The stenoses were categorized into six groups by the effect on %WT (each group representing progressive 20% decrements in %WT from control), and individual and pooled regression analyses were performed on data from six of the dogs having multiple data points to evaluate the shape (linear or curvilinear) of the relationships between MBF and changes in %WT. Transmural contractile function was highly sensitive to acute reductions in MBF, especially reductions in the subendocardium. The shape of the normalized subendocardial MBF-%WT relation was mildly curvilinear by regression analysis (quadratic equation, gamma = -0.75x2 + 2.15x -0.39, r2 = 0.92). Likewise, mean transmural and midmyocardial MBF correlated well and closely with changes in %WT. Subepicardial MBF, however, correlated poorly with changes in %WT, there being no change in subepicardial MBF until %WT had been reduced more than 50%.