Comparison of in vitro laboratory analyses with the fertility of cryopreserved stallion spermatozoa.

Assessing the fertilizing potential of a semen sample is important for effective stallion management and for rapid progress in evaluating new cryopreservation technologies. Unfortunately, sperm motility does not estimate fertility well. These experiments established assays to measure cell viability, acrosomal integrity and mitochondrial function for cryopreserved stallion spermatozoa, using flow cytometry, and determined the variability associated with these assays. Correlations between results for these laboratory assays and stallion fertility were also determined. The inter-assay variability for visual motility, computer assisted motility, and sperm velocity, sperm viability, percent viable-acrosome intact cells and mitochondrial function of cells were all similar, however, intra-assay variability was lower for flow cytometric assays than for motility assays. The reliability of all assays were >0.72, except for sperm velocity (0.32). Although visual motility and the straightness of sperm motility conducted 90 min after thawing were correlated with seasonal fertility (0.56 and 0.55, respectively), data from no single assay were correlated with first-cycle fertility rates (P > 0.05). Best models using data from multiple assays explained 66 to 73, 76 to 89 and 79 to 94% of the variability in fertilizing potential, when two, three and four variables were included, respectively. Caution is required in interpreting these data, as only a few stallions were evaluated and relatively few mares were bred to each stallion, however, they do indicate that using a few rapid and inexpensive sperm assays, we can begin to understand factors important in stallion sperm fertilizing capacity, and we can use these assays to more effectively evaluate new methods for cryopreserving stallion spermatozoa.

Ventricular preload alters intravascular and extravascular resistances of coronary collaterals.

Coronary collateral blood flow is determined by both the collateral vessel resistance and a waterfall mechanism. The aim of this study was to determine which of these two mechanisms predominates during alteration of ventricular preload. The left anterior descending coronary artery of 12 anesthetized dogs was cannulated, and the distal vasculature was completely embolized with 25-micron diameter microspheres. Retrograde blood flow (RBF) was collected when the cannula was opened to the atmosphere, and the outflow tubing height was adjusted to provide a variable back pressure. RBF is back pressure-dependent at higher back pressures, and the slope in this region of the constructed pressure-flow relationship determines the collateral conductance. The transition point between the back pressure-dependent and a back pressure-independent region indicates a waterfall pressure impinging on the collateral vessels. At a left ventricular diastolic pressure of 9.3 mmHg, mean RBF, collateral conductance, and the collateral waterfall pressure were 7.3 ml/min, 0.175 ml.min-1.mmHg-1, and 30.1 mmHg, respectively. Corresponding values when preload was reduced to 3.5 mmHg were 9.3 ml/min, 0.186 ml.min-1.mmHg-1, and 23.7 mmHg, all changes being significant. Mean contribution to the overall increase in RBF was 0.5 ml/min for the conductance and 1.2 ml/min for the waterfall mechanism (P less than 0.05), or 29 and 71%, respectively. The results indicate that the extravascular resistance mechanism mediates the collateral flow response to a greater degree than the intravascular resistance during variations in preload. The increase in slope of the conductance portion of the relationship was not accompanied by a concomitant increase in slope of the back pressure-independent region. These data further support a collateral waterfall, and not collateral vessel compliance, as the basis for the back pressure-independent portion of the pressure-flow relationship.

A nonflow basis for the vulnerability of the subendocardium.

The functional consequences of a transmural gradient of metabolism in the heart were studied in 19 dogs. The technique of retrograde blood flow diversion after coronary occlusion was used to deplete the ischemic myocardium of blood flow. Blood flow was uniformly and equally depleted in all layers, averaging 0.044 ml/min per g. With oxygen supply a controlled variable, transmural differences in metabolic demand can be addressed. In groups of dogs severe myocardial ischemia was induced for periods of 20 to 90 minutes. No necrosis was noted after 20 minutes of ischemia. Beginning at 30 minutes of blood flow depletion, necrosis progressed from the endocardium toward the epicardium in a "wave front" pattern. At 90 minutes of ischemia, approximately 70% of the area at risk was necrotic. Thus, the relative vulnerability of the endocardium as compared with the epicardium is due to nonflow factors, and probably dictated by transmural differences in metabolic activity. It would appear that myocardial metabolism as compared with blood flow occupies a primary and overriding role during the first 20 minutes of ischemia. Furthermore, differences in transmural metabolism also dictate subendocardial vulnerability for ischemic periods greater than 20 minutes, irrespective of blood flow. The role of blood flow in these events may be to modulate the rate of the transmural wave front of progressing necrosis after 20 minutes of ischemia.

Lateral border zone: quantitation of lateral extension of subendocardial infarction in the dog.

This study was undertaken to quantitate the lateral extension that occurs concomitantly with the transmural extension of a subendocardial infarction. A subendocardial infarct was produced in 12 dogs by a 40 minute temporary coronary artery occlusion. Infarct extension was induced 7 days later by permanent occlusion of the same vessel. Regional myocardial blood flows confirmed that ischemia had been produced with both coronary artery occlusions. The vascular boundaries between the normally perfused and ischemic beds were defined by perfusion with different-colored Microfil solutions. The extent of subendocardial infarction and subsequent transmural and lateral extensions were assessed by point counting of histologic specimens. The initial temporary occlusion produced a 30.0 +/- 4.2% transmural infarct and the subsequent permanent occlusion a 29.2 +/- 3.5% transmural extension in a risk region of 39 +/- 4 g. Lateral extension was not measured in four dogs because the initial subendocardial infarct was patchy with markedly irregular lateral borders. In eight dogs the size of the measured lateral infarct extension from each lateral margin from two histologic sections was 0.63 +/- 0.013 cm2. The area of both lateral extensions was 1.7 +/- 0.1% of the cross-sectional area of its risk region as determined by planimetry. Using a model of the risk region, the mass of the lateral extension was estimated to be 1.4 +/- 0.3 g or 3.5 +/- 0.6% of the region at risk. Thus, at the lateral margin of a subendocardial infarct there is a border zone that is small relative to the size of the region at risk and infarcted myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of vasopressin on the coronary circulation: reserve and regulation during ischemia.

In 18 dogs, intracoronary infusion of vasopressin produced a 40% reduction in coronary flow without significantly affecting systemic hemodynamics. The blood flow reduction occurred in a uniform transmural pattern without evidence of a gradient. The reduction in coronary flow resulted in a decrease in regional contractility as determined by isometric strain gauge arches. The decrease in regional contractility was transiently reversed by bolus injection of adenosine into the perfusion line. This suggests that the reduction of blood flow due to vasopressin was causing ischemia. Evidence for ischemia was also supported by measurements of local vein and tissue lactate production. Despite the apparently ischemic conditions, the vascular bed demonstrated evidence for significant reserve and regulation. Pressure-flow relationships performed under control and during vasopressin infusion demonstrated that the coronary vasculature retained its ability to regulate or defend a given level of coronary flow over a range of coronary perfusion pressures. Vasopressin produced a mild decrease in the peak hyperemic flow after a 15-s coronary occlusion and shortened the duration of reactive hyperemia. These overall findings are compatible with a predominant vasoconstrictor effect on the distal coronary vasculature. A role for a myogenic factor in the control of the coronary circulation is suggested, which is amplified by vasopressin.

Improvement of coronary blood flow by augmentation of coronary vascular compliance.

Coronary blood flow occurs predominantly during the diastolic period of the cardiac cycle. This study investigated the effects of increasing the diastolic coronary perfusion pressure by artificially increasing the epicardial coronary capacitance function, using a buffer chamber. The left anterior descending (LAD) coronary artery was cannulated in six dogs and perfused by tubing via the carotid artery. A significant stenosis was produced with a screw clamp, resulting in a distal coronary pressure of about 35 mm Hg. A buffer chamber was placed on the perfusion line distal to the stenosis to buffer the distal coronary perfusion pressure. Myocardial blood flow as measured by microspheres showed a 39.6% increase in blood flow during buffered perfusion as compared to nonbuffered perfusion: 0.415 +/- 0.279 versus 0.316 +/- 0.238 ml/min/g. The calculated diastolic pressure time index (DPTI) increased 54.1% during buffered perfusion. Flow increased significantly in the endocardial and mid-wall layers but not in the epicardium. It is concluded that coronary blood flow can be augmented by increasing the coronary capacitance function in this model.

Newer concepts in the pathophysiology of ischemic heart disease.

Thus the thrust of these studies suggests that blood flow is the overwhelming factor in determining the consequences of the imbalance of oxygen supply and demand. Moreover, the factors that determine the requirements for tissue survival in the presence of deep ischemia are not the same as those shown for the normal myocardium in figure 1. In deep ischemia, contraction ceases, and metabolism shifts from aerobic to anaerobic pathways. Survival rather than contractile function then becomes the agenda. Not only does supply tend to overshadow demand in determining extent of transmural necrosis, but the anatomical pattern of supply precisely delineates the region at risk following a coronary occlusion as well as the ultimate extent of infarction. These views are summarized in the model presented in figures 12 and 13. The anatomic distribution of the ligated artery determines the lateral limits of the ischemic region (Fig. 12) and thus the lateral extension of necrosis (Fig. 13). The extension of the necrosis across the heart wall depends largely on the status of perfusion within the ischemic region. Extension of an infarct, should it occur, has to be explained by other mechanisms. These might include: (i) vascular obstruction in adjacent vascular systems that were not involved in the first occlusion, (ii) relative ischemia in the normal tissue surrounding the ischemic tissue due to an increased wall stress at the demarcation between contracting and noncontracting tissue, or (9) interruption of vessels supplying large interdigitations of normal tissue within the originally ischemic tissue due to changes associated with the process of infarction of ischemia. Alternatively, much that is called extension of infarction may involve more of the wall transmurally without lateral extension. Additional features of the development of myocardial infarction in figures 12 and 13 include: (i) the development of collateral vessel function resulting in an increased capacity to supply the ischemic area, and (ii) a redistribution of collateral blood flow from necrotic to surviving myocardium within the ischemic area. Thus, as coronary collaterals develop, collateral blood flow becomes increasingly heterogeneous within the ischemic area. Following a coronary occlusion, blood flow is reduced more in the subendocardium, and infarction occurs. Resistance to flow in infarcting tissue increase and causes a redistribution of flow to adjacent surviving layers of myocardium that life toward the epicardium. The process continues and combined with the enlargement of collateral vessels results in a sufficient flow to the epicardial layers so that they may survive.

Thallium-201 accumulation during reperfusion of ischemic myocardium: dependence on regional blood flow rather than viability.

These experiments in dogs were designed to determine whether the use of thallium 201 (TI-201) accumulation in patients during the reperfusion phase after streptokinase lysis of an intracoronary thrombus is a function of coronary blood flow or a function of myocardial viability. The left anterior descending coronary artery was occluded for 60 minutes in open-chest dogs, and the immediate TI-201 accumulation and regional blood flow (MBF) using microspheres was measured in 2 groups: 10 minutes after reperfusion in 9 dogs (group A) and 24 hours after reperfusion in 6 dogs (group B). There was an 80% or greater reduction in MBF in the subendocardium during ischemia in both groups of dogs, and it was inferred that the subendocardium was destined to become necrotic in group A and had become necrotic in group B dogs. The ratio of TI-201 accumulation to MBF in the tissue that had been ischemic was not significantly different from the ratio in normal tissue despite MBF being in the normal range in group A (n = 7, 2 dogs excluded because of reactive hyperemia) and being markedly decreased in group B. Thus, the immediate TI-201 distribution was related to MBF, and caution is recommended in its use to assess myocardial salvage in the early reperfusion phase after streptokinase lysis of intracoronary thrombi. These data suggest that the intramyocardial accumulation of TI-201 is predominantly a passive process and independent of Na-K ATPase.

Flow into ischemic myocardium and across coronary collateral vessels is modulated by a waterfall mechanism.

If a coronary artery is ligated and the distal end cannulated, blood flows retrograde from the cannula when vented to the atmosphere. By varying the height of the outflow tubing, and thereby changing the outflow pressure, pressure-flow relationships can be constructed. We used this technique in eight dogs to assess the characteristics of blood flow into ischemic myocardium. Above a back pressure of 10 mm Hg, increasing back pressure resulted in a decrease of retrograde blood flow. However, below a back pressure of about 10 mm Hg (10.7 +/- 2.7 mm Hg), alterations in back pressure did not result in changes in retrograde blood flow (back pressure-independent region). The transition at 10 mm Hg is interpreted as the critical waterfall pressure in ischemic myocardium. In another group of eight dogs, the ischemic bed was completely embolized with 25-micron sized microspheres to prevent RBF from entering the tissue as back pressure was raised. Pressure-flow relationships performed in this group revealed a back pressure-independent region that extended to approximately 20 mm Hg (23.0 +/- 2.5 mm Hg). This behavior of the pressure-flow relationship is consistent with a waterfall phenomenon on the collateral vessels. To the extent that collateral vessels in the dog are mainly epicardial in location, the findings suggest that extravascular pressures of 20 mm Hg can occur in the more superficial layers of the heart. In addition, the waterfall on the collaterals indicates that this mechanism can operate on nonvenous vessels. Our results suggest separate waterfall phenomena operating on the collateral vessels (20 mm Hg) and on the vessels in the ischemic myocardium (10 mm Hg).

Myocardial micronecrosis produced by microsphere embolization. Role of an alpha-adrenergic tonic influence on the coronary microcirculation.

Microspheres approximately 25 or 50 micrometers in diameter were systemically embolized from the left ventricular cavity. The number of microspheres given was empirically chosen to minimize the possibility of more than one microsphere lodging in an arteriole (3 mg/kg), yet was sufficient to allow for adequate histological assessment. The dogs were sacrificed after 24 hours, and focal areas of myocytolytic necrosis were noted in the myocardium. Groups of dogs were given pretreatment with drugs 10 minutes before embolization. Dogs pretreated with phentolamine (n = 8) and prazosin (n = 2) did not reveal any areas of myocardial necrosis after embolization with 25-micrometers microspheres. Cardiac lesions were also prevented in four of five dogs pretreated with verapamil. In contrast, cardiac lesions were not prevented by pretreatment with yohimbine (n = 2), dipyridamole (n = 3), propranolol (n = 2), or atropine (n = 2). Drug pretreatment with phentolamine or verapamil was not able to prevent cardiac lesions after embolization with 50-micrometers microspheres. Furthermore, despite a greater number of microspheres physically present in the subendocardial layer, the necrotic lesions were more frequent in the mid-wall and epicardial layers. Lesions produced by 25- or 50-micrometers emboli were also significantly smaller in the endocardium. Systemic embolization with microspheres excluding the coronary circulation did not produce cardiac lesions. We conclude that mechanical interruption of the coronary circulation with a 25-micrometers microsphere may be a necessary but not sufficient condition to produce cardiac necrosis. An alpha 1-adrenergic mechanism is also involved in the production of these lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effect of verapamil and nitroglycerin on collateral blood flow.

The effects of intracoronary verapamil and nitroglycerin on collateral blood flow were compared under conditions where coronary perfusion pressure was held constant with a servopump and the systemic effects of the drugs were minimal. Both drugs were infused into 12 anesthetized dogs after occlusion of the left anterior descending coronary artery (LAD) and regional myocardial blood flow (MBF) was measured using microspheres. Before the LAD occlusion, the myocardium not perfused by the LAD was labeled to permit calculation of the fraction of tissue normally perfused in the LAD samples and corrections for collateral flow. The central ischemic zone contained 2.5 +/- 0.3% normally perfused myocardium and a 4-mm border zone contained 26.8 +/- 4.3% normal myocardium. This border zone contained 10% of the total tissue supplied by the LAD. The MBF in the central ischemic zone increased from 0.101 +/- 0.019 to 0.113 +/- 0.022 ml/min/g after verapamil infusion (NS) and to 0.149 +/- 0.024 ml/min/g after nitroglycerin (p less than 0.01). Uncorrected MBF in the border zone increased significantly after infusion of both verapamil (0.469 +/- 0.085 ml/min/g, p less than 0.01) and nitroglycerin (0.398 +/- 0.056, p less than 0.05). When corrections were made for interdigitating normal tissue in the border zone, only the MBF after nitroglycerin was significantly increased. Thus, nitroglycerin significantly increased the collateral blood flow to ischemic tissue in the central ischemic and border zones, but verapamil did not.

Acute myocardial infarct extension into a previously preserved subendocardial region at risk in dogs and patients.

In this study we quantitated the region of preserved myocardium between a subendocardial myocardial infarct (SEMI) and the endocardium in dogs and determined whether this preserved zone was within the region at risk and whether infarct extension could occur in this region. We also evaluated whether a similar subendocardial region exists in patients with SEMI. A 40-minute temporary occlusion of the left anterior descending coronary artery (LAD) in eight dogs resulted in a 35 +/- 5% transmural infarct with 8 +/- 1% subendocardial preservation as assessed by point-counting of the histologic specimens. In vivo perfusion of coronary vessels with Microfil showed that this preserved subendocardial zone was within the region at risk. The preserved subendocardial zone had significantly fewer cell layers in the dogs ventilated with room air than in dogs ventilated with 100% oxygen (8 +/- 4 vs 19 +/- 4, p less than 0.001), which suggests that diffusion from the ventricular cavity was the mechanism of cell preservation. In contrast, the inspired oxygen concentration did not influence the size of the SEMI. Reocclusion of the LAD for 24 hours in an additional eight dogs, 1 week after a SEMI had been created by a 40-minute temporary occlusion, resulted in both subendocardial and subepicardial extension involving 5 +/- % and 29 +/- 9%, respectively, of the transmural myocardium at the infarct center. Subendocardial infarct extension of a similar dimension to that in dogs ventilated on 100% oxygen was observed in postmortem material from eight patients with infarct extension. The preserved layers of subendocardium presumably receive sufficient nutrients from the ventricular cavity to maintain the viability of this region during temporary, but not permanent, reduction of blood supply from the coronary arteries.

Analysis of coronary collateral structure, function, and ischemic border zones in pigs.

The purpose of this study was to compare coronary collateral structure and function in pigs with those in dogs and to analyze the distribution of collateral blood flow across the lateral and transmural border zones in the pig. After acute occlusion of the left anterior descending coronary artery (LAD) in 26 anesthetized open-chest pigs, minimal collateral blood flow was indicated by retrograde flow (0.2 +/- 0.1 ml/min) and microsphere-myocardial blood flow (0.005 +/- 0.001 ml X min-1g-1). Postmortem injection of the distal LAD followed by clearance of the heart demonstrated few tiny collateral structures and negligible collateral filling of other arteries. In contrast to dogs, pigs showed no measurable gradient of collateral blood flow across the transmural border zone, and pigs showed no change in collateral blood flow or its transmural distribution during retrograde drainage of collateral blood flow or elevated left ventricular filling pressures. Pigs showed higher myocardial blood flow in the lateral border than in the center of the ischemic zone. As in the dog, however, this gradient of blood flow across the lateral border zone was accounted for by overlap between occluded LAD branches and unoccluded coronary arterial branches rather than by preferential collateral perfusion of the lateral border of the ischemic zone. We conclude that the pig has a homogeneous distribution of collateral blood flow across the transmural and lateral border zones after acute coronary occlusion but that the minimal collateral circulation limits the usefulness of the pig as a model of ischemic heart disease.

The microcirculation of the human heart: end-capillary loops with discrete perfusion fields.

We studied 10 autopsied human hearts by perfusing colored Microfil into separate coronary arteries to define organization of capillaries at the borders between two perfusion fields. Sections of "cleared" myocardium were examined with epiillumination at the grossly identified borders of Microfil perfusion. In two- and three-color-injected hearts, the capillaries were arrayed in a pattern of arcades and loops without connections between separately perfused capillary beds. In hearts perfused through only one coronary artery, the capillaries were organized into tufted loops at the border. These findings contrast with the microcirculatory pattern in canine skeletal muscle and brain, in which heterologous capillaries are focally interconnected. We conclude that the human microcirculation is composed of end-capillary loops that supply discrete perfusion fields. This pattern of unconnected heterologous capillary beds suggest that there is no obvious anatomic arrangement of the microcirculation that could account for a significant ischemic lateral border zone in human myocardial infarctions.

Contractile reserve and left ventricular function in regional myocardial ischemia in the dog.

Contractile activity remaining in a region made ischemic by acute occlusion of the left anterior descending coronary artery (LAD) was assessed in dogs relative to its role in maintaining left ventricular (LV) function. Compensatory increases in contractility of normal myocardium were eliminated by treating all dogs with reserpine (3 mg/kg) to deplete their catecholamine stores. LV function was determined by measuring stroke volume while increasing the LV filling pressure with a shunt from the aorta to left atrium. Heart rate and mean aortic pressure were kept constant. LV function was studied after occlusion of the LAD alone and after the selective infusion of potassium chloride (1 mEq/ml) into the LAD to raise the regional extracellular potassium concentration to 30 mEq/ml. The reduction in LV function induced by LAD ligation was less than the reduction caused by abolishing contraction in the entire zone supplied by the LAD with infusion of potassium. The totally cardioplegic zone induced by potassium amounted to 20.3-39.8% of the LV mass. At an LV end-diastolic pressure of 12 mm Hg, stroke volume (SV) was reduced in proportion to the size of the cardioplegic zone: -SV (% volume) = -1.55% (% of LV mass) + 120.1 (r = -0.69, p less than 0.005). Thus, a dyskinetic zone of 35% of the left ventricle reduced stroke volume by 34% when adrenergic compensation was blocked. We conclude that residual transmural contractility exists in the ischemic region of myocardium subserved by an obstructed LAD and contributes significantly to LV function.

Increased ventricular fibrillation threshold with severe myocardial ischemia.

The ventricular fibrillation threshold (VFT) is a measure of myocardial electrical vulnerability to exogenous electrical stimulation. Previous studies have shown that the VFT is inversely related to ischemia. We studied the relation of the VFT to myocardial blood flow (MBF) during ischemia produced by interruption of blood flow to the left anterior descending coronary artery, and severe ischemia produced by retrograde bleeding an ischemic segment of myocardium. The VFT with severe ischemia (8.6 +/- 1.3 mA; MBF 0.024 +/- 0.01 ml/min/gm tissue), although lower than nonischemic control values (14.2 +/- 2.0 mA; 0.76 +/- 0.05; both p less than 0.05), was higher than that obtained with moderate ischemia (4.6 +/- 0.9 mA; 0.15 +/- 0.02 ml/min/gm; both, p less than 0.05). Thus the relationship between the VFT and MBF is nonlinear. Interventions which cause the VFT to rise may do so by worsening rather than improving regional MBF.

Newer concepts in the pathophysiology of ischemic heart disease.

A model of myocardial ischemia based on the balance of oxygen demand and supply is presented. Ischemia is invariably the result of a limited coronary blood flow (supply), but increased oxygen consumption is often cited as a factor causing an imbalance of demand and supply. The role of contractility in ischemia, however, has been overemphasized, and inotropic agents such as glycosides and isoproterenol frequently have effects on supply that overshadow their effects on myocardial oxygen consumption. With deep ischemia leading to infarction, supply also tends to overshadow demand in determining the extent of transmural necrosis. Moreover, the anatomic pattern of supply precisely delineates both the region at risk following coronary occlusion and the ultimate extent of the infarction. These views are presented in anatomic models of myocardial ischemia and infarction.

The effects of the coronary capacitance on the interpretation of diastolic pressure-flow relationships.

The effects of coronary capacitance on instantaneous pressure-flow (P/F) relationships were analyzed using a theoretical model of coronary flow during diastole that included capacitance. The magnitude of the discrepancy between actual intramural and instantaneously derived P/F relationships was predicted to be dependent on the ratio of two natural decay constants (central aortic decay constant/intrinsic coronary decay constant). The effects of coronary capacitance are eliminated using constant pressure conditions. The instantaneous (dynamic) and constant pressure (static) P/F relationships were compared experimentally using a reservoir to provide constant pressure perfusion during prolonged diastoles in heart blocked dogs. In the presence of coronary tone, zero flow pressure intercepts (Pzf) of 27.1 +/- 6.6 and 11.0 +/- 3.0 mm Hg were obtained under dynamic and constant pressure conditions respectively, P less than 0.001. After maximal vasodilation, Pzf of 14.2 +/- 4.5 mmHg and 10.7 +/- 2.4 mmHg were obtained under dynamic and constant pressure conditions, respectively, P = NS. Pzf derived under constant pressure conditions were independent of the state of coronary vasomotor tone with a value about 11 mmHg. The slopes of the dynamic P/F relationships tended to be greater than those derived from constant pressure conditions. This may suggest an additional component of increasing coronary resistance during diastole that could not be readily assessed under dynamic conditions. We conclude that coronary capacitive effects and resistance changes during diastole severely limit the interpretation of instantaneous dynamic P/F relationships. Diastolic coronary perfusion ceases at about 11 mm Hg and is independent of coronary tone when capacitive effects are eliminated.