Subendocardial Flow Research Articles

Regeneration of myocardial phosphocreatine in pigs despite continued moderate ischemia.

The effects of 1 hour of mild and moderate reductions in coronary blood flow on myocardial high-energy phosphate levels were evaluated. Thirty anesthetized pigs were instrumented with left anterior descending arterial and venous catheters, crystals for instantaneous wall thickness, and a fluid-filled occluder. Measurement of myocardial blood flow was performed with microspheres, and a series of myocardial biopsies also was performed. In 10 pigs, overall coronary blood flow was lowered by 22%, with a fall in subendocardial-to-subepicardial flow ratio from 1.11 to 0.54 and in wall thickening from 33% to 15%. Subendocardial flow fell 48%. Coronary blood flow and thickening were constant during 1 hour of ischemia. Phosphocreatine (mumol/g wet wt) in the subendocardial third of the ischemic zone fell from 7.6 to 3.8 at 5 minutes of ischemia (p less than 0.005 versus control) and returned to normal (7.9) at 60 minutes (p = NS), despite ongoing ischemia. Subendocardial ATP (mumol/g wet wt) fell slowly from 4.3 and leveled off at 2.1 at 60 minutes of ischemia (p less than 0.001 versus control). Similar regeneration of phosphocreatine was found in seven additional pigs, with a 43% transmural reduction in coronary blood flow and a 66% reduction in subendocardial flow. No significant changes in ATP and phosphocreatine were noted in two different control groups (n = 13 pigs). The regeneration of phosphocreatine despite ongoing ischemia and low ATP levels was not related to changes in myocardial oxygen demand or consumption, or in regional function during the period of ischemia. This may reflect 1) a successful downregulation of the energy needs of the ischemic myocardium to maintain cell viability, or 2) a metabolic abnormality in the ability of the cells to produce ATP primarily or by use of phosphocreatine.

Effect of tachycardia on regional function and transmural myocardial perfusion during graded coronary pressure reduction in conscious dogs.

The purpose of the present study was to examine subendocardial flow and function during graded coronary pressure reduction to determine the effect of tachycardia on the lower autoregulatory pressure limit (critical coronary pressure) in unanesthetized dogs. During atrial pacing at a rate of 200 beats/min, subendocardial flow measured by radioactive microspheres averaged 1.55 +/- 0.34 ml/min/g and remained unchanged as pressure was reduced over the autoregulatory plateau from 84 +/- 10 to 59 +/- 7 mm Hg. Further reductions in coronary pressure to below a critical coronary pressure of approximately 60 mm Hg were associated with concomitant reductions in subendocardial flow and the endocardial-epicardial flow ratio during tachycardia. Although regional function remained constant over the autoregulatory plateau, there was a rightward shift of the coronary pressure-function relation during ischemia in response to a steady-state increase in rate from 100 to 200 beats/min. Reductions in regional wall thickening began when coronary pressures reached 38 +/- 7 mm Hg at a heart rate of 100 beats/min and 61 +/- 6 mm Hg at a heart rate of 200 beats/min (p less than 0.005). Similar critical coronary pressure values were obtained for subendocardial segment shortening. Relations between subendocardial flow and myocardial function measured by both transmural wall thickening and subendocardial segment shortening were linear during pacing at a heart rate of 200 beats/min with relative reductions in wall thickening related to reductions in subendocardial flow on a nearly one-to-one basis. The results of this study demonstrate that there is a shift in the lower limit of subendocardial autoregulation during tachycardia as manifest by the onset of subendocardial ischemia at a higher distal coronary artery pressure. The shift in critical coronary pressure relates to an increase in resting flow requirements due to increased demand and diminished subendocardial vasodilator reserve at any given coronary pressure secondary to a reduction in the time available for diastolic subendocardial perfusion during tachycardia.

Enhanced myocardial salvage by maintenance of microvascular patency following initial thrombolysis with recombinant tissue plasminogen activator

The aim was to examine the value of a subthrombolytic maintenance infusion of recombinant double chain tissue plasminogen activator (BW t-PA, Duteplase) in preserving microvascular coronary flow following initial thrombolysis. Coronary arterial thrombi were induced by a copper coil (placed under fluoroscopic control) in the canine left anterior descending coronary artery. Complete vessel occlusion occurred within 10-15 min of coil placement. Following 90 min of thrombotic occlusion, animals received one of three treatments: group 1, vehicle 0.9% saline; group 2, t-PA 1.0 X 10(6) IU.kg-1.h-1 for 1 h; group 3, t-PA 1.0 X 10(6) IU.kg-1.h-1 for 1 h followed by 0.12 X 10(6) IU.kg-1.h-1 throughout the 2 h reperfusion period. Radiolabelled microspheres were administered to assess microvascular coronary flow at various time points throughout the experimental period. Experimental subjects were beagle dogs of either sex (n = 30), weight 8.9-14.3 kg. Main vessel patency (assessed fluoroscopically) was achieved within 40.0(SEM 4.0) min and 37.0(3.1) min for group 2 and group 3 animals respectively. Group 1 animals did not reperfuse. Full microvascular coronary flow was achieved following the lytic infusion of t-PA. However, microvascular flow to the ischaemic zone was significantly reduced at the end of the 2 h reperfusion phase in group 2 animals despite "aggressive" anticoagulation with heparin throughout the reperfusion period: subendocardial flow decreased from 0.74(0.14) to 0.24(0.08) ml.min-1.g-1; subepicardial flow decreased from 0.82(0.13) to 0.36(0.09) ml.min-1.g-1, p less than 0.05. Microvascular coronary flow to the ischaemic zone was better preserved following the maintenance infusion of t-PA given throughout the reperfusion phase: subendocardial flow decreased from 0.95(0.07) to 0.50(0.10) ml.min-1.g-1; subepicardial flow decreased from 0.73(0.04) to 0.52(0.08) ml.min-1.g-1. Thrombolytic reperfusion led to salvage of the ischaemic myocardium, with infarct/risk ratio decreasing from 75.0(10.0)% in group 1 to 46.3(11.0)% in group 2, p less than 0.05. Further salvage of the ischaemic myocardium followed a lytic plus maintenance infusion of t-PA, with infarct/risk ratio decreasing to 35.5(6.7)% but this did not reach statistical significance. t-PA consistently achieved main vessel reperfusion within 40 min (mean) of instituting therapy in our model, leading to marked salvage of ischaemic myocardium. The data also suggest that maintenance infusion of t-PA helps preserve microvascular coronary flow throughout reperfusion and tends to reduce infarct size further.

Changes in diameter of coronary narrowings and translesional hemodynamics after intracoronary nitroglycerin

The effect of intracoronary nitroglycerin on coronary stenosis dimensions and translesional hemodynamics was evaluated in 38 subjects (74 stenoses) referred for diagnostic coronary arteriography. Quantitative coronary arteriography was performed with standard Newtonian fluid dynamic equations used to estimate transstenotic gradients. Since intracoronary nitroglycerin can induce significant myocardial hyperemia (increased flow velocity), with increased translesional pressure gradients and a decrease in distal intraluminal pressure, the potential effect on subendocardial flow distribution was also analyzed. Minimum stenotic diameter significantly increased postnitroglycerin (NTG) (preNTG 1.42 vs postNTG 1.82 mm, p < 0.01), with a decrease in relative percent diameter stenosis (preNTG 45.7 vs postNTG 40.7%, p 0.05). When changes in minimum stenotic diameter were analyzed according to stenosis severity (quartiles), the greatest effect was noted in those lesions with the least severe stenosis (quartile no. 1, 0.49 vs quartile no. 4, 0.32 mm, p < 0.05). If coronary blood flow velocity remains at baseline values (4 cm/s), intracoronary nitroglycerin was predicted to significantly decrease transstenotic pressure gradients (preNTG 1.01 vs postNTG 0.82 mm Hg, p < 0.05), with the greatest change shown in severe lesions (quartile no. 4, preNTG 3.79 to postNTG 2.28 mm Hg, p < 0.01). Accelerated coronary flow velocity (myocardial hyperemia) increased calculated translesional pressure gradients (4 cm/s, 0.82 mm Hg vs 20 cm/s, 8.00 mm Hg, p < 0.01), despite simultaneous stenotic vasodilation. Hemodynamic obstruction was particularly dependent on coronary flow velocity in the most severe stenoses (quartile no. 4, 4 cm/s, 2.28 vs 20 cm/s, 28.78 mm Hg, p < 0.01). Therefore, intracoronary nitroglycerin causes significant stenosis vasodilation, which under baseline (resting) conditions would partially alleviate hemodynamic obstruction. However, since this medication also produces transient increased coronary flow velocity (myocardial hyperemia), transstenotic pressure gradients may actually increase, with the potential for transmyocardial flow maldistribution and subendocardial ischemia.

Phasic regional myocardial inflow and outflow: comparison of theory and experiments

We developed a theory for regional blood flow in the beating heart and validated it with measurements of coronary arterial inflow and venous outflow in the open-chest anesthetized dog. The model used measured aortic, left ventricular, and coronary sinus pressures as input data under control conditions and during long diastoles induced by vagal stimulation. A nonlinear two-compartment lumped model for each transmural layer was obtained by spatial averaging a continuum description of the myocardial microcirculation based on morphometric measurements and appropriate fluid and vascular mechanics principles. The chief results and conclusions of the study are 1) an intramyocardial time constant on the order of 1 s is required to explain the phase opposition between inflow and outflow; 2) capillary and venous perfusion are in phase with arterial pressure, and arterial flow is out of phase with arterial pressure except in superficial intramural layers; 3) subendocardial retrograde systolic flow increases with increased contractility and time constants and decreased arterial pressure; and 4) endocardial capillary and venule volume change by 5.5 and 10%, respectively, during the control cardiac cycle.

Effect of Pinacidil on Myocardial Blood Flow in the Presence of a Coronary Artery Stenosis

This study examined the effect of pinacidil on transmural distribution of myocardial blood flow during normal conditions and in the presence of a coronary artery stenosis. Studies were performed in 11 awake dogs; blood flow was measured with radioactive microspheres. Two doses of pinacidil were administered to decrease mean arterial pressure (MAP) by approximately 10 mm Hg (low dose, 0.18 +/- 0.02 mg/kg) and 20 mm Hg (high dose, 0.32 +/- 0.03 mg/kg). Measurements were performed during unimpeded arterial inflow and with two levels of coronary stenosis that limited blood flow to approximately 60% above (moderate stenosis) and approximately 30% above basal flow (severe stenosis). With no stenosis, coronary flow increased 227 +/- 17% after low-dose and 321 +/- 31% after high-dose pinacidil (each p less than 0.01). During control conditions, subendocardial (endo) flow exceeded subepicardial (epi) flow (endo/epi ratio = 1.33). This ratio was not changed by low-dose pinacidil but decreased to 0.93 after high-dose pinacidil (p less than 0.05). During high-dose pinacidil, a coronary stenosis caused uniform reduction of blood flow across the left ventricular wall, with no further significant change in the ratio of endo/epi flow. With low-dose pinacidil, both moderate and severe degrees of stenosis caused redistribution of flow away from the subendocardium similar to that observed with high-dose pinacidil. Although a stenosis that limited the increase in mean coronary flow after pinacidil administration to 162% of the predrug control value had a 95% probability of not causing a decrease in absolute subendocardial flow, the data suggest that pinacidil could have potential for aggravating subendocardial ischemia in severe occlusive coronary artery disease.

Quantitative assesment of reductons in subendocardial and full-thickness regional flow reserve during progresssive coronary stenosis using ultrafast tomography

Quantitative assesment of reductons in subendocardial and full-thickness regional flow reserve during progresssive coronary stenosis using ultrafast tomography

Relative reductions in subendocardial and fullthickness flow during pharmacologic vasodilation as an index of functional stenosis severity

Relative reductions in subendocardial and fullthickness flow during pharmacologic vasodilation as an index of functional stenosis severity

Model-based analysis of transmural vessel impedance and myocardial circulation dynamics

The basic structure of a model of the coronary circulation has been developed to explain the relationship between transmural perfusion dynamics and intramyocardial mechanics. The model is in the form of a topologically isomorphic network representation and incorporates experimentally measured time-varying perfusion and intramyocardial pressure sources as driving inputs to the model. The intramyocardial vessels are treated as nonlinear impedance elements possessing regional external pressure-dependent resistance and capacitance. Three circuit branches, perfusing the epicardial, subepicardial, and subendocardial muscle layers, are mathematically modeled and are used to predict time-dependent flow within the left ventricular myocardium. The phasic coronary blood flow characteristics predicted by the model exhibit waveform patterns that correlate qualitatively with those patterns measured experimentally. In addition, the pressure-dependent vascular capacitance induces a sustained (out of phase with arterial inflow) venous systolic flow. The model also exhibits retrograde systolic subendocardial flow and stop-flow pressure, which are dependent on coronary resistive and capacitive properties and on the perfusion pressure decay time constant. Furthermore, the results predict an abrupt decrease in subendocardial flow with perturbation of either arteriolar or capillary bed compliance. The model describes time-dependent intramyocardial properties that have been confusing and controversial in the understanding of coronary circulation dynamics. Several steps are identified that are expected to improve and refine the model significantly.

Transmural distribution of calcium accumulation and glucose uptake in the calcium paradox in the rat left ventricle

The calcium paradox was induced in the isolated perfused rat heart and the transmural distributions of glucose uptake and calcium accumulations were determined using 2-deoxy-D-[ 3H]glucose and 45Ca 2+ as tracers. The regional distribution of coronary flow was measured using radiolabelled microspheres. A significant transmural gradient was observed in left ventricular glucose uptake both in the control and the calcium paradox hearts: subendocardial and subepicardial glucose uptake rates were 5.70 ± 0.65 μmol/min/g protein (mean ± s.e.m.) and 4.29 ± 0.35 μmol/min/g protein ( P < 0.05) in the control hearts, and 8.64 ± 0.79 μmol/min/g protein and 4.09 ± 0.71 μmol/min/g protein ( P < 0.01) in the paradox hearts. This increase in subendocardial glucose uptake in the calcium paradox was also significant ( P < 0.05), while the average left ventricular calcium accumulation was about 10-fold in the paradox hearts compared to the controls ( P < 0.001). A steep transmural gradient was observed in the paradox hearts, calcium influx being 4.72 ± 0.57 μmol × 10 −1/min/g protein in the subendocardium and 14.02 ± 0.93 μmol × 10 −1/min/g protein in the subepicardium ( P < 0.001). The subendocardium received initially 30% more perfusion than subepicardium ( P < 0.01), but the subendocardial flow during the calcium depletion and replenishment periods was only 40% of that in the subepicardium ( P < 0.001) and the average myocardial flow was reduced by c. 60% ( P < 0.001). The data show clear transmural differences in the alterations associated with the calcium paradox. This suggests that the calcium paradox induced myocardial injury is unevenly distributed across the left ventricular wall, this uneven distribution possibly being due to regional differences in the damage of mitochondrial energy production.

Studies on prolonged acute regional ischemia: II. Implications of progression from dyskinesia to akinesia in the ischemic segment

This study analyzed the pattern of regional wall motion in 58 dogs undergoing 4 to 6 hours of left anterior descending coronary artery occlusion. Regional wall motion was measured by ultrasonic crystals and ischemic muscle either remained dyskinetic (-40% of control systolic shortening, n = 26) or progressed toward akinesia (less than 20% of control systolic shortening or greater than 50% reduction in passive lengthening, n = 32). Ten dogs underwent unmodified blood reperfusion. Regional blood flow (radioactive microspheres), histochemical damage (triphenyltetrazolium chloride staining), and mitochondrial function were determined. Hearts showing persistent dyskinesia had more collateral flow (12 versus 2 ml/100 gm/min, p less than 0.05), less histochemical damage (26% versus 63% area at risk/area of nonstaining, p less than 0.05), and better retention of mitochondrial oxidative phosphorylation capacity (adenosine triphosphate, 622 versus 444 nmol/mg protein/min, p less than 0.05), and tended toward mitochondrial calcium accumulation (48 versus 64 nmol/mg protein). Unmodified blood reperfusion after 4 hours of ischemia produced prompt akinesia (-2% +/- 3% systolic shortening) and was associated with increased edema (82% water content), caused the low-reflow phenomenon (19% control subendocardial flow, 13 ml/100 gm/min), and increased histochemical damage (69% triphenyltetrazolium chloride nonstaining, p less than 0.05). These findings suggest that persistent dyskinesia during early ischemia (first 6 hours) may reflect a relatively optimistic sign, as regression to akinesia occurs in muscle with less collateral flow, more impaired mitochondrial function, worsened calcium homeostasis, and more severe histochemical and ultrastructural damage. These observations imply that careful evaluation of ischemic wall motion may provide a valuable insight into potential muscle salvage.

Stress-shortening relations and myocardial blood flow in compensated and failing canine hearts with pressure-overload hypertrophy.

Serial changes in left ventricular (LV) size and function during the adaptation to chronic pressure overload and the transition to pump failure were studied in 16 conscious dogs (aortic bands placed at 8 weeks of age). Echocardiographic data at baseline and at 3, 6, 9, and 12 months after banding revealed a progressive increase in LV mass in all dogs. In six dogs with LV pump failure, there was a progressive decline in circumferential fiber shortening (29 +/- 4% at 12 months); this was significantly less than that seen in five littermate controls (38 +/- 3%, p less than 0.05). The average LV to body weight ratio in this group was 9.8 +/- 2.7 g/kg. In 10 dogs without pump failure (compensated LVH group), shortening exceeded that seen in the controls (43 +/- 4%, p less than 0.05); the LV to body weight ratio was 7.7 +/- 1.0 g/kg. At 12 months (cardiac catheterization), the LV end-diastolic pressure was higher in the failure (25 +/- 15 mm Hg) than in the compensated group (8 +/- 5 mm Hg, p less than 0.05); mean systolic stress was also higher in the failure group (313 +/- 67 g/cm2) than in the compensated group (202 +/- 53 g/cm2, p less than 0.05). The transmural distribution of myocardial blood flow was measured (at 12 months) with the radioactive microsphere technique; flow data were then related to an index of demand (a stress-time index). There was preferential blood flow to the subendocardial layers in the control (endo/epi = 1.28) and compensated hearts (endo/epi = 1.10), but in the failure group there was a relative decrease in subendocardial flow (endo/epi = 0.92). However, the absolute values for subendocardial flow in the normal, compensated, and failure groups were 77 +/- 54, 125 +/- 48, and 113 +/- 64 ml/min/100 g; the stress-time indexes in the subendocardial shell were 38 +/- 11, 74 +/- 19, and 93 +/- 34 g sec.10(2)/cm2/min. Despite what appears to be a marginal balance between blood flow and the stress time index in the failure group, the myocardial high energy phosphates were not depleted and the inoptropic state was not depressed. In this model of LV hypertrophy, the observed differences in fiber shortening can be explained on the basis of the inverse afterload-shortening relation; pump failure was due to an inadequate LV hypertrophy with afterload excess.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of atrial natriuretic peptide on transmural blood flow and reactive hyperemia in the presence of flow-limiting coronary stenosis in the awake dog: evidence for dilation of the intramural vasculature.

The effects of atrial natriuretic peptide (ANP) on transmural myocardial blood flow distribution and the reactive hyperemic response in the presence and absence of flow-limiting coronary stenosis were examined in chronically instrumented conscious dogs. Ten-second coronary occlusion without subsequent flow restriction resulted in marked reactive hyperemic responses (Doppler flow probes), mean flow debt repayment was 481 +/- 55%. When the 10-second coronary occlusions were followed by a 20-second partial restriction that allowed normal preocclusion coronary inflow, the subsequent reactive hyperemia was significantly augmented, mean flow debt repayment was 938 +/- 91% (p less than 0.05). Pretreatment with ANP (3 micrograms/kg) did not alter the flow debt repayment after a 10-second occlusion without restriction (474 +/- 30%, NS) but attenuated the augmentation of reactive hyperemia resulting from the 20-second inflow restriction, flow debt repayment (613 +/- 66%, NS). Regional myocardial blood flow to the ischemic region was measured during restricted inflow after a 10-second coronary occlusion before and after ANP pretreatment. Before ANP, subendocardial flow decreased (0.54 +/- 0.04 ml/min/g) and subepicardial flow significantly increased (1.03 +/- 0.12 ml/min/g) when compared with the nonischemic zone (subendocardial, 1.03 +/- 0.09 ml/min/g; subepicardial, 0.87 +/- 0.09 ml/min/g, p less than 0.05), indicating maldistribution of the restricted inflow. The resultant subendocardial-to-subepicardial ratio in the ischemic region was significantly decreased when compared with the nonischemic region (0.56 +/- 0.03 vs. 1.18 +/- 0.04, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The quotient of mean arterial pressure and heart rate predicts hypoperfusion of collateral-dependent myocardium

This study tested the hypothesis that the quotient of mean arterial pressure (MAP) and heart rate (HR) (pressure - rate = PRQ) effectively predicts myocardial hypoperfusion in regions of myocardium supplied with blood via collateral vessels. Regression analysis of data gathered in a study of the effects of halothane and atrial pacing on the distribution of myocardial blood flow has discovered a strong relationship between the PRQ and the inner-to-outer flow ratio in the collateral-dependent zone (R = 0.78). A significant relationship was also found between PRQ and the ratio of subendocardial blood flow in the ischemic zone to subendocardial flow in the normally perfused zone (R = 0.61). These ratios demonstrate that hypoperfusion of the inner layers of the collateral-dependent zone occurred during the condition of hypotension combined with tachycardia; while normal flow distribution was present if MAP exceeded HR. Halothane (1 % end-tidal) did not alter the distribution of coronary flow, indicating that halothane does not cause a coronary steal in this model. The results of this study support the concept that the PRQ is an effective predictor of myocardial hypoperfusion when flow to ischemic zones is delivered by collateral vessels in nonfailing, canine hearts.

The Effect of the Thromboxane A2/Prostaglandin Endoperoxide Receptor Antagonist SQ 30,741 on Myocardial Infarct Size and Blood Flow During Myocardial Ischemia and Reperfusion

The effect of the thromboxane A2 (TXA2) receptor antagonist SQ 30,741 on infarct size and myocardial blood flow during coronary occlusion and reperfusion was determined. In anesthetized dogs, the left circumflex coronary artery (LCX) was occluded and after 10 min a continuous infusion of SQ 30,741 (1 mg/kg + 1 mg/kg/h, i.v.) or saline was begun. After 90 min of LCX occlusion, the LCX was reperfused for 5 h and infarct size was then determined. Myocardial blood flows before, during, and after occlusion were determined using radioactive microspheres. SQ 30,741 resulted in a significant decrease in infarct size (34% +/- 6% of left ventricular area at risk) compared to controls (60% +/- 9%). Cardioprotection was also found with SQ 30,741 when infarct size was normalized for both area at risk and predrug collateral flow. The protective effect of SQ 30,741 occurred without an increase in collateral flow. At 1 h postreperfusion, subendocardial flow was significantly higher in SQ 30,741-treated animals (109 +/- 15 ml/min/100 g) compared to controls (71 +/- 16 ml/min/100 g). SQ 30,741, in the dose resulting in infarct size reduction, produced a 95% inhibition of platelet TXA2 receptors throughout the experiment as measured by dose-dependent inhibition of the ex vivo platelet shape change response to U-46,619, a TXA2 mimetic. Thus, a dose of SQ 30,741 that results in TXA2 blockade also results in myocardial salvage without changes in collateral flow.

Reductions in regional myocardial function at rest in conscious dogs with chronically reduced regional coronary artery pressure.

We have examined the temporal response of regional subendocardial function in conscious chronically instrumented dogs following implantation of a circumflex ameroid occluder. Collateralization was limited by ligation of epicardial anastamoses between the circumflex and adjacent coronary arteries at the time of instrumentation. Sonomicrometrically measured regional function in the circumflex coronary artery became depressed relative to that in the left anterior descending coronary artery bed under resting conditions with the onset of an aortic-circumflex pressure gradient of 15 +/- 2.9 mm Hg (mean +/- SEM). At the time of total ameroid occlusion, the ratio of circumflex to left anterior descending coronary artery function fell to 68 +/- 8% of control, with mean circumflex coronary pressure decreasing to 60 +/- 1.6 mm Hg. Following ameroid occlusion, distal coronary pressure increased, and circumflex function recovered towards control but remained depressed relative to that in the left anterior descending coronary artery for 2-4 weeks. Measurements of regional subendocardial perfusion suggested a dissociation between subendocardial flow and function prior to but not following coronary occlusion by the ameroid. We conclude that this model results in reductions in regional function that are relatively prolonged and are not readily attributable to subendocardial infarction or a critical reduction in resting coronary flow. The data suggest that functional adaptations in response to gradually developing coronary occlusion are more complex than those associated with acute reductions in coronary artery pressure and flow.

β-Adrenoceptor stimulation and blockade during myocardial ischemia in dogs: effect on cardiac O 2 supply and consumption

The effect of β-adrenoceptor blockade and activation on ischemic regional and microregional myocardial O 2 supply/consumption parameters was assessed in 28 open chest, anesthetized dogs. Ten minutes after LAD occlusion, dogs were given i.v. saline, 2 mg/kg propranolol, 0.2 mg/kg pindolol, or 1 μg/kg per min isoproterenol. Coronary blood flow was determined using radioactive microspheres before and 2 h after LAD occlusion while O 2 supply/consumption parameters were determined using microspectrophotometry. Ischema resulted in a 66% reduction in subendocardial flow in controls in the ischemic zone and no experimental treatment significantly altered this flow. Pindolol resulted in a significant improvement in the ischemic regional subendocardial/subepicardial flow ratio (from 0.69 in the control ischemic region to 0.88 during pindolol treatment). O 2 extractions were significantly increased and O 2 consumptions were significantly depressed in the ischemic regions of all groups. O 2 extractions were increased to a lesser degree in the ischemic region with the use of pindolol and proprandolol. Proprandolol and pindolol both significantly decreased the proportion of veins with low (0–20%) O 2 saturations in the ischemic region indicating an improved microregional distribution of blood flow and/or O 2 consumption within the ischemic region.

Effect of early coronary artery reperfusion on infarct development in a model of low collateral flow.

To characterise collateral blood flow patterns after coronary artery occlusion in the rat and to determine whether tissue can be salvaged by reperfusion in this model, anaesthetised rats were subjected to 20, 30, 40, 60 min of coronary occlusion followed by 24 h of reperfusion or 24 h of permanent occlusion. Relative regional blood flow was measured by radioactive microspheres after 10 min of occlusion in rats undergoing 30 min of occlusion plus reperfusion and in those undergoing 24 h of permanent occlusion. The area at risk was determined by in vivo injection of fluorescent microspheres and necrosis delineated by in vitro tetrazolium staining. Tracings of heart slices were planimetered and the area of necrosis and transmural extent of the infarct measured. Blood flow in the area at risk during occlusion was similar in both the reperfused and permanent occlusion groups. In the 30 min group mean(SEM) subendocardial flow was reduced to 13(5)% of normal and subepicardial flow to 9(3)% and in the permanent occlusion group to 11(2)% and 8(3)% respectively. As delineated by fluorescent microspheres the area at risk was transmural in all rats; however, infarct size expressed as a percentage of the area at risk increased as the duration of occlusion increased. In rats reperfused up to 30 min after occlusion the area of necrosis as a percentage of the area at risk was significantly decreased compared with that in the permanent occlusion group (36.4(9.2)% in rats with 30 min occlusion plus 24 h reperfusion and 78.6(7.4)% in rats with permanent occlusion).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vasodilator reserve persists despite tachycardia and myocardial ischemia.

During myocardial ischemia, we tested whether coronary blood flow would increase in response to tachycardia, thereby employing known coronary flow reserve. We instrumented the left anterior descending (LAD) coronary circulation in anesthetized pigs and performed three sets of experiments while coronary pressure was controlled and several heart rate increases were produced. Pacing-induced tachycardia at normal LAD pressure was characterized by increased LAD flow and myocardial oxygen consumption, without production of lactate. Tachycardia at a mean LAD pressure of 38 mmHg was associated with a lower, fixed coronary flow and oxygen consumption. At average heart rates of 90 and 150 beats/min, LAD flow was 19.6 and 19.4 ml/min and corresponding myocardial blood flows were 0.59 and 0.54 ml X g-1 X min-1. Lactate was produced at all rates and local myocardial function declined progressively. Coronary flow at low LAD pressure doubled during tachycardia when intracoronary adenosine was added. The increase to the subepicardium was greater than 100%, whereas subendocardial flow changed little. There is persistent coronary flow reserve during moderately severe myocardial ischemia, even when metabolic demand is increased by tachycardia. This reserve, however, is predominantly subepicardial.

Effect of the New Specific Bradycardic Agent AQ-A39 (Falipamil) on Coronary Collateral Blood Flow in Dogs

The effect of two doses (0.5 and 1.0 mg/kg i.v.) of a new specific bradycardic agent, AQ-A39 (5,6-dimethoxy-2-[3- [( alpha- (3,4,-dimethoxy)phenylethyl]methyl-amino)propyl]phthalimidine hydrochloride), on three indices of collateral function--retrograde pressure, retrograde flow, and tissue blood flow (radioactive microspheres)--was studied in anesthetized dogs following acute occlusion of the left anterior descending coronary artery. AQ-A39 produced a significant (p less than 0.05) dose-related decrease in heart rate without any other hemodynamic changes. Retrograde flow and subendocardial blood flow were significantly increased by the lower dose of AQ-A39, whereas retrograde pressure, retrograde flow, and midmyocardial and subendocardial flow were increased by the higher dose. Atrial pacing to the control heart rate eliminated the beneficial effects of AQ-A39 on collateral function. These results suggest that an increase in collateral perfusion may be one mechanism by which AQ-A39 alleviates myocardial ischemia.