Extravascular Resistance Research Articles

Myocardial perfusion distribution and coronary arterial pressure and flow signals: clinical relevance in relation to multiscale modeling, a review

Coronary artery disease, CAD, is associated with both narrowing of the epicardial coronary arteries and microvascular disease, thereby limiting coronary flow and myocardial perfusion. CAD accounts for almost 2 million deaths within the European Union on an annual basis. In this paper, we review the physiological and pathophysiological processes underlying clinical decision making in coronary disease as well as the models for interpretation of the underlying physiological mechanisms. Presently, clinical decision making is based on non-invasive magnetic resonance imaging, MRI, of myocardial perfusion and invasive coronary hemodynamic measurements of coronary pressure and Doppler flow velocity signals obtained during catheterization. Within the euHeart project, several innovations have been developed and applied to improve diagnosis-based understanding of the underlying biophysical processes. Specifically, MRI perfusion data interpretation has been advanced by the gradientogram, a novel graphical representation of the spatiotemporal myocardial perfusion gradient. For hemodynamic data, functional indices of coronary stenosis severity that do not depend on maximal vasodilation are proposed and the Valsalva maneuver for indicating the extravascular resistance component of the coronary circulation has been introduced. Complementary to these advances, model innovation has been directed to the porous elastic model coupled to a one-dimensional model of the epicardial arteries. The importance of model development is related to the integration of information from different modalities, which in isolation often result in conflicting treatment recommendations.

Effects of amlodipine and adenosine on coronary haemodynamics: in vivo study and numerical simulation

Amlodipine (AMLO) is a calcium channel blocker with vasodilating properties, in which the specific effects on the coronary circulation are not fully known. Coronary flow velocity–pressure (F/P) curves were obtained at rest and during administration of AMLO (10 mg to 20 mg iv) or adenosine (ADO, 1 mg ic) in 10 normal subjects (six women, age 48 ± 14 years). F/P curves were reproduced in a numerical simulator of systemic and coronary circulations (CARDIOSIM©) by adjustment of coronary resistance ( > or < 100 μm diameter vessels) and extravascular resistance applied to smaller vessels at endocardial (ENDO), middle and epicardial (EPI) myocardial layers. Best matching of in silico to in vivo curves was achieved by trial and error approach. ADO induced 170% and 250% increase in coronary flow velocity CFV and F/P diastolic slope as compared to 80% and 25–30% increase induced by AMLO, respectively. In the cardiovascular model, AMLO effects were predicted by progressive reduction of>100 μm vessels resistance from EPI to ENDO. ADO effects were mimicked by reducing resistance of both>100 μm and < 100 μm vessels, progressively from EPI to ENDO in the latter. Additional reduction in extravascular resistance avoided to impose a transmural gradient of vasodilating effect for both drugs. Numerical simulation predicts vasodilating effects of AMLO mainly on larger arteries and of ADO on both>and < 100 μm vessels. In vivo F/P loops could be completely reproduced in silico by adding extravascular resistance reduction for both drugs. Numerical simulator is useful tool for exploring the coronary effects of cardioactive drugs.

Coronary wave intensity during the Valsalva manoeuvre in humans reflects altered intramural vessel compression responsible for extravascular resistance

Our aim was to investigate the effect of altered cardiac-coronary interaction during the Valsalva manoeuvre (VM) on coronary wave intensity and the response of coronary microvascular resistance. In 13 patients, left ventricular (P(LV)) and aortic pressure were measured during catheterization, together with intracoronary pressure and blood flow velocity (U) via a dual-sensor guide wire advanced into an angiographically normal coronary artery. Signals were analysed for the following phases of VM: baseline (B1), onset of strain (S1), sustained strain (S2), onset of release (R1), maximal response during recovery (R2), and baseline after VM. The immediate effects of VM were most evident from diastolic P(LV) (LVDP), which increased from 11.0 ± 2.3 to 36.4 ± 2.7 mmHg between B1 and S1 and fell from 28.3 ± 3.4 to 8.3 ± 1.9 mmHg between S2 and R1. Wave intensities and rate pressure product (RPP) were only minimally affected at these transient phases, but coronary wave energies decreased by about 50% and RPP by 38% from S1 to S2, together with a 30% depression of LVdP/dt. All signals were restored to baseline values during the recovery. U did not vary significantly throughout the VM. Despite the depressed cardiac performance during VM strain, microvascular resistance, calculated with LVDP as backpressure, decreased by 31% from B1 to S2, whereas an increase via metabolically induced vasoconstriction was expected. Since coronary U remained essentially constant despite the marked reduction in oxygen consumption, microvascular vasoconstriction must have been compensated by a decrease in the contraction-mediated impediment on coronary blood flow, as confirmed by the reduced coronary wave energies.

Prevalence of Paroxysmal Atrial Fibrillation Depending on the Regression of Left Ventricular Hypertrophy in Arterial Hypertension

Arterial hypertension (HTN) represents one of the major causes of atrial fibrillation, a cardiac arrhythmia with high prevalence and comorbidity. The aim of this study was to investigate whether paroxysmal atrial fibrillation can be treated by the regression of left ventricular hypertrophy achieved by antihypertensive therapy. Included in the present study were 104 patients who had had HTN for more than 1 year. None of them suffered from coronary heart disease. All patients were investigated by 24-h Holter ECG and echocardiography at baseline and after a mean of 24 months. Patients were divided into two groups: group A consisted of those (53.8%) who showed a regression of the left ventricular muscle mass index (LVMMI) during the follow-up (154.9+/-5.1 vs. 123.5+/-2.8 g/m(2)), and group B those (45.2%) who showed a progression of LVMMI (122.2+/-3.2 vs. 143.2+/-3.2 g/m(2)). In group A the prevalence of atrial fibrillation decreased from 12.5% to 1.8% (p<0.05), while it was increased in group B from 8.5% to 17.0%. The left atrial diameter was reduced following antihypertensive therapy in group A from 39.1+/-5.3 mm to 37.4+/-4.6 mm (p<0.01) and increased in group B from 37.0+/-0.7 mm to 39.0+/-0.9 mm (p<0.01). We conclude that a regression of the left ventricular muscle mass leads to a reduction of left atrial diameter and consecutively to a decrease in the prevalence of intermittent atrial fibrillation. This may be explained by a better left ventricular diastolic function following decreased vascular and extravascular resistance of the coronary arteries. This relation shows the benefits of causal antihypertensive therapy for the treatment of paroxysmal atrial fibrillation.

The influence of plaque orientation (pericardial or myocardial) on coronary arterial remodeling

Background: Many systemic, regional and lesion factors have been identified which may influence arterial remodeling, but little is known about the importance of extravascular resistance to vessel enlargement. As myocardial systolic splinting may significantly affect vessel expansion the effect of plaque orientation on arterial remodeling in eccentric coronary atherosclerotic lesions was examined. Methods: Using intravascular ultrasound imaging to obtain cross-sectional vessel area (VA), plaque area (PA) and lumen area (LA), remodeling in eccentric left anterior descending coronary artery lesions was compared which predominantly involved the pericardial or free arc (P, n=25) and the myocardial side (M, n=40) of the vessel wall. Normalized vessel area (NVA, VA lesion/VA reference) was compared as a continuous and categorical variable (positive>1.05, intermediate 0.95–1.05, negative<0.95) as well as remodeling index (RI, VA lesion−VA reference/PA lesion−PA reference). Results: The two groups were well matched for clinical and lesion characteristics known to affect remodeling. Reference segments areas were similar in the two groups; while lesion LA was also similar, in the pericardial group there was significantly greater lesion PA (P 12.78±0.72, M 10.26±0.50 mm 2, P<0.05) and VA (P 15.71±0.90, M 12.82±0.57 mm 2, P<0.05) demonstrating enhanced compensatory remodeling. Outward remodeling was significantly greater in P than in M by both NVA (P 1.03±0.03, M 0.86±0.03, P<0.01) and RI (P 0.02±0.07, M −1.10±0.32, P<0.01). Positive, intermediate and negative remodeling occurred in nine, nine and seven lesions in P and in four, ten and 26 lesions in M (P<0.01). Conclusions: Remodeling compensates more for plaque growth in eccentric coronary lesions which are surrounded by the pericardium than those surrounded by the myocardium. Extravascular resistance appears to influence arterial remodeling.

Perioperative Myocardial Ischemia: Pathophysiology and Does it Really Matter

Perioperative Myocardial Ischemia: Pathophysiology and Does it Really Matter

PET measurement of the coronary flow reserve and microcirculatory function.

This review article discusses some of the potentially beneficial effects of calcium antagonists on the coronary microcirculation. These include their vasodilating action on coronary resistance vessels as well as their effects on extravascular resistance (i.e. intramyocardial pressure). Examples are presented of how the non-invasive measurement of myocardial blood flow and flow reserve by means of positron emission tomography (PET) can contribute to the understanding of the effects of drug treatment on the coronary microcirculation. The action of calcium antagonists on the coronary microcirculation can contribute to explain the efficacy of these drugs against ischemia and ischemia-reperfusion damage.

Histology of root rot of flax seedlings (Linum usitatissimum) infected by Fusarium oxysporum f.sp. lini

The histology of root rot of flax seedlings infected by Fusarium oxysporum f.sp. lini was studied using semi-thin sections of plastic-embedded roots. Within two days, the fungus colonised the root cap cell layers by intercellular and intracellular growth. Attempted intercellular penetration of root cap cells via the middle lamella induced the formation of appositions next to penetrating hyphae. Other cells next to invading hyphae collapsed, which was accompanied by swelling of the cells neighbouring the collapsing cells. Invasion of the root cap and growth towards the protodermis seemed retarded to some extent by the natural sloughing off of root cap cell layers. The protodermis and cortex were reached and penetrated in four days, which was followed by rapid and massive colonisation of the entire root tip. The protoxylem was reached in eight days. From eight to sixteen days after inoculation, the lower parts of the roots were colonised throughout and the cortical region was degraded. Colonised tissues were severely plasmolyzed. Heavily colonised roots were hollowed out, the only remaining tissues being the epidermis and exodermis outside, and remainders of the colonised xylem inside. Upward spread of root rot was restricted in the period studied to the first 10 mm from the root tip, the upper parts of the root and the hypocotyl being unaffected except for invasion through lateral roots infected at their respective tips. Mature roots with a well-developed epidermis and exodermis were not invaded from outside. Disease development was similar in partially resistant ‘Hermes’ and susceptible ‘Regina’, except for rot development that was consistently slightly more extensive in the susceptible cultivar. Distinct extravascular resistance factors were not detected in ‘Hermes’, suggesting that extravascular resistance in flax to F. oxysporum f.sp. lini is of a quantitative nature.

Microcirculation: what is the role of calcium antagonists?

This review article discusses some of the potentially beneficial effects of calcium antagonists on the coronary microcirculation. These include their vasodilating action on coronary resistance vessels as well as their effects on extravascular resistance (i.e. intramyocardial pressure). Examples are presented of how the non-invasive measurement of myocardial blood flow and flow reserve by means of positron emission tomography can contribute to the understanding of the effects of drug treatment on the coronary microcirculation. The action of calcium antagonists on the coronary microcirculation may help explain the efficacy of these drugs against ischaemia and ischaemia-reperfusion damage.

Clinical significance of coronary flow reserve: effect of papaverine and exercise.

The clinical significance of coronary flow reserve (CFR) was evaluated after pharmacological (papaverine) and physiological (exercise) vasodilation in patients with coronary artery disease (CAD). CFR was determined using parametric imaging in 10 patients with normal coronary arteries (group 1) and in 10 with CAD (group 2). Contrast density and mean appearance time were measured (region of interest = 249 pixels) in the perfusion beds of the left circumflex and the left anterior descending coronary arteries at rest, 45 s after 10 mg intracoronary papaverine, and during supine bicycle exercise. CFR was calculated from coronary perfusion after papaverine divided by perfusion at rest and coronary perfusion during exercise divided by perfusion at rest. Perfusion zones in patients with CAD were subdivided into regions supplied by a non-stenosed (group 2a) and a stenosed (group 2b) coronary artery. In control patients, heart rate increased from 75 beats/min at rest to 125 beats/min during exercise, and in patients with CAD from 63 to 107 beats/min, respectively. Mean aortic pressure showed a significant increase during exercise in both groups. Mean pulmonary artery pressure increased significantly during exercise from 19 to 28 mmHg in control patients and from 22 to 42 mmHg in the CAD group (P < 0.001). Coronary driving pressure (mean aortic minus diastolic pulmonary artery pressure) tended to increase during exercise in the control group (from 90 to 101 mmHg, NS) and remained nearly unchanged in patients with CAD (from 92 to 94 mmHg, NS). In the control group, CFR was significantly higher during exercise than after papaverine (4.0 versus 3.5, respectively; P < 0.01). However, coronary resistance (coronary driving pressure divided by coronary flow index) was similar after papaverine and during exercise. In patients with CAD, papaverine-dependent CFR was significantly reduced in the perfusion zone of the stenosed (2.1) but not of the non-stenosed coronary artery (3.0). In contrast, CFR during exercise was significantly decreased in both perfusion zones (2.5 in non-stenosed arteries and 1.5 in stenosed vessels). In control patients, CFR is slightly but significantly larger during exercise than after papaverine because of the exercise-induced increase in coronary driving pressure. In contrast, CFR is smaller during exercise than after papaverine in patients with CAD, most probably as a result of secondary mechanisms such as exercise-induced narrowing of stenosed vessels or an increase in extravascular resistance. Thus, CFR based on papaverine appears to be of limited value for assessing the functional significance of a stenotic lesion.

Localization ability, latent period and wilting rate in eleven carnation cultivars with partial resistance to Fusarium wilt

The latent periods, wilting rates and percentages of diseased plants were analyzed for 11 carnation cultivars after root and after stem inoculation with race 2 of Fusarium oxysporum f.sp. dianth. There was no conclusive evidence for the presence of an independent extravascular resistance mechanism, except for ‘Lena’ plants in which, additional to the vascular resistance components, independent root-bound factors causing retardation of the colonization and wilting process were found. A large variation was observed in the ablity of the cultivars to localize the pathogen in the vascular tissue shortly after infection of the xylem. This ability was positively correlated with the latent period, and negatively with the wilting rate and final disease index. In resistant cultivars, secondary compartmentalization of the fungus higher up in the stem was also observed. After stem inoculation, differences among the cultivars in localization ability and wilt-retarding actors could be identified at an early stage by comparing the precentages of non-colonized plants or the percentages of plants lacking vascular discolouration.

Subendocardial coronary compression in beating dog hearts is independent of pressure in the ventricular lumen

Ventricular decompression has been shown to have little effect on either the magnitude or transmural distribution of the extravascular resistance in the small hearts of the cat or rabbit. This study tests whether that independence from ventricular pressure also occurs in the large heart of the dog, which should be more representative of the human. We measured regional myocardial flow in each in situ dog heart during three conditions: normally beating, vented beating, and arrest. Hearts were perfused at constant pressure and maximally dilated with 0.4-1.0 mg/min ic adenosine. Total coronary blood flow was measured with an electromagnetic flowmeter, and regional flow was assessed with radiolabeled microspheres. Although arrest resulted in more than a doubling of flow to the inner layer, greatly reducing ventricular pressure by venting had no significant effect on subendocardial flow. Subepicardial flow was minimally affected by either venting or arrest. We conclude that both the magnitude and the transmural distribution of extravascular resistance in the large heart of the dog is unrelated to the pressure in the ventricular lumen.

An Angiographic Study of Intracardiac Coronary Arteries from Human Autopsy Hearts: Their Clinicopathologic Significance and Characterization During Transmural Myocardial Infarction

In this study of human autopsy hearts, coronary arteries were divided by morphologic criteria into classes A (branching-type) and B (straight-type) arteries. Infarcted hearts and normal hearts were investigated mainly by means of coronary angiography, as well as by gross and histologic examinations. Transmural myocardial infarction originated in the inner half of the myocardial layer, which was predominantly supplied by class A arteries, followed by gradual extension to the outer layer. The early infarcted focus revealed an angiographically avascular state. This may have been the result of shrinkage of the peripheral branches of class A arteries due to increased extravascular resistance rather than to arteriolar obstruction by small thrombi and/or leukocyte plugs. By contrast, class B arteries remained patent and were almost entirely free from such phenomena. They usually penetrated the infarcted focus to drain into the papillary muscles and trabeculae carnae. As the process of myocardial infarction progressed, various patterns of vascular reactions corresponding to the healing phase were demonstrated by these branches within the infarcted foci. The passive response of class A arteries during acute ischemia characterized the early myocardial lesion. Subsequently, neovascularization from the surviving class B arteries in the infarcted focus occurred as a part of the formation of granulation tissue. Newly formed small arteries from class A arteries also participated in this reaction at the marginal area of the lesion. These well-coordinated vascular reactions revealed in greater detail the initiation and progression of the healing process and were reflective of the clinical prognosis.

Physiology and Pathophysiology of the Heart

This comprehensive and updated Second edition is an impressive contribution to the fundamentals of basic science of the heart. The editor has assembled 48 chapters written by experts and wellknown researchers. Eight new chapters, a precious and timely addition to the first edition, include comprehensive discussions on contractile proteins of cardiac muscle, contractile proteins of smooth muscle, cyclic nucleotides and protein kinase in smooth muscle, calcium-activated ion currents in cardiac muscle, developmental changes in adrenergic modulation, endothelial cell interactions with vascular smooth-muscle cells, myocardial infarction and free radical effects on the heart, and extravascular coronary resistance. The basic factors affecting the function of the normal and diseased heart are evaluated by a comprehensive multidisciplinary approach including membrane biophysics, electrophysiology, physiology, pathophysiology, pharmacology, biochemistry, and ultrastructure. Adroitly written chapters, such as chapter 31 on hormonal cardiac performance, deal with topics of special interest to diabetologists and cardiologists alike. Diabetic cardiomyopathy and

Effect of heart rate and myocardial contractile force on coronary resistance.

The effect of the heart rate and myocardial contractile force on the extravascular resistance to blood flow of the left anterior descending coronary artery (LAD) was evaluated in 15 mongrel dogs anesthetized with sodium pentobarbital. The LAD was maximally dilated by intracoronary infusion of adenosine, which precluded the influence of vasomotor tone. Increases in the heart rate and myocardial contractile force decreased coronary blood flow in the absence of a change in coronary perfusion pressure. The changes in mean coronary resistance showed a significant linear relationship to changes in developed tension. The changes in coronary resistance caused by varying the heart rate and contractile force were so small that a normal coronary vascular tree could easily compensate for the increase in resistance. However, it is supposed that with critical stenosis of the vascular tree even a small increase in resistance might cause deleterious effects on coronary blood flow.

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.

Interaction of plasma colloid osmotic pressure and joint fluid pressure across the endothelium-synovium layer: Significance of extravascular resistance

Fluid exchanges between blood and a synovial joint cavity across two membranes in series—synovial capillary wall (fenestrated) and synovial intima (modified connective tissue). The relation between transsynovial absorption of intraarticular Krebs solution (flow Q ̇ s ) and plasma colloid osmotic pressure π p was investigated in rabbit knees perfused at constant blood pressure. Intraarticular pressure P j was independently controlled. Linear relations between transsynovial flow and plasma colloid osmotic pressure established that transsynovial flow obeys the Starling hypothesis. However osmotic conductance, d Q ̇ s dπ p , increased 3.9 times when P j was raised from 6 cm H 2O or subatmospheric pressure to 18 cm H 2O—the “yield phenomenon.” Comparison of the effects of π p and capillary pressure revealed no major change in the osmotic reflection coefficient of the blood—joint barrier to albumin upon raising P j. The large increase in osmotic conductance was predicted quantitatively by a previous model (prediction 3.8 ×) based on increases in extravascular (intimal) conductance as a function of extravascular pressure. It is argued that capillary endothelium is not the sole significant hydraulic resistance in this pathway. In the terminology of Intaglietta and de Plomb (1973) synovial capillaries are functionally intermediate between “tubes” and “tunnels.”

Effects of AR-L 115 BS (Sulmazol), a new cardiotonic agent, in coronary artery disease: Improved ventricular wall motion, increased pump function and abolition of pacing-induced ischemia

AR-L 115 BS (Sulmazol) is a new noncatechol, nonglycosidic cardiotonic agent. In 17 patients with significant coronary artery disease, the influence of AR-L 115 BS on hemodynamics and regional wall motion was investigated under the following conditions: 1) control, 2) the immediate postpacing period without medication, and 3) the postpacing period under the peak influence of AR-L 115 BS, 2 mg/kg intravenously. During the postpacing phase without medication, all patients developed ischemia (angina, ST segment alterations, increase of mean left ventricular end-diastolic pressure from 13 to 30 mm Hg), left ventricular pump function diminished and overall regional wall motion showed a tendency to decrease (p greater than 0.05). However, during the postpacing period with AR-L 115 BS medication, ischemia was abolished (no angina; mean left ventricular end-diastolic pressure decreased to 13 mm Hg; hemodynamic variables returned to control levels and left ventricular pump function showed some improvement while overall regional wall motion showed tendencies to improve. A comparison of alterations of hemodynamics and regional wall motion during the postpacing phase without medication with those under the influence of AR-L 115 BS shows that overall left ventricular pump function and regional wall motion improved while angina and an increase in left ventricular end-diastolic pressure were prevented. It is concluded that AR-L 115 BS improves left ventricular pump function and regional wall motion in coronary artery disease without inducing ischemia, probably by means of a reduction in extravascular resistance.

Coronary perfusion pressure during experimental cardiopulmonary resuscitation

Systemic blood flow during cardiopulmonary resuscitation may result from alterations in intrapleural pressure (IPP), with the heart serving only as a passive conduit. Chest compression with simultaneous lung inflation (C + SI) or with abdominal binding may also increase vascular pressures and cerebral flow. Our study was done to evaluate the effects of C + SI with and without abdominal binding on coronary perfusion pressure (CPP) during CPR. Micromanometric pressures were recorded in 7 dogs during ventricular fibrillation (VF) and CPR to evaluate CPP (aortic minus right atrial pressure). During chest compression alone, aortic (AoP) and right atrial (RAP) pressures did not differ significantly. During relaxation, AoP (15 +/- 4 mm Hg) was greater than RAP (3 +/- 2 mm Hg; P less than 0.001) and diastolic CPP averaged 12 +/- 4 mm Hg. C + SI significantly increased AoP, RAP, and IPP, but did not improve systolic or diastolic CPP. Tight abdominal binding during chest compression alone or during C + SI also increased AoP and RAP and caused a slight but insignificant decrease in diastolic CPP. Extravascular resistance to coronary flow during VP has been shown to average 28 mm Hg in the in vitro heart. Our study indicates that CPPs calculated during CPR do not reach sufficient values to overcome the resistance offered by the fibrillating myocardium. Interventions which increase IPP, intravascular pressures, and carotid flow do not improve CPP or, by inference, coronary flow.

Effect of acute regional ischemia on pressure in the subepicardium and subendocardium.

The effects of acute ischemia on regional intramyocardial pressure were studied in eight open-chest dogs. Aortic, left ventricular, subepicardial, and subendocardial pressures were measured with catheter-tip micromanometers. During the control period subendocardial pressure during systole (180 +/- 13 mmHg; mean +/- SE) was higher than left ventricular intracavitary pressure (137 +/- 9 mmHg; P less than 0.001). Subepicardial pressure during systole was lower (95 +/- 6 mmHg; P less than 0.001). Acute ischemia caused a reduction of subendocardial pressure during systole to levels below left ventricular systolic pressure (92 +/- 7 mmHg vs. 116 +/- 6 mmHg; P less than 0.01). Ischemia also caused a reduction of systolic subepicardial pressure to 67 +/- 2 mmHg (P less than 0.001). After reperfusion all pressures returned nearly to control values. During diastole subendocardial pressure during the control period (13 +/- 1 mmHg) was high than left ventricular end-diastolic pressure (6 +/- 1 mmHg; P less than 0.001). Subepicardial pressure during diastole (29 +/- 2 mmHg) was higher than subendocardial pressure and left ventricular end-diastolic pressure (P less than 0.001). Acute ischemia had little or no effect on subendocardial pressure during diastole, whereas it caused a reduction of subepicardial diastolic pressure to 16 +/- 1 mmHg (P less than 0.001). Reperfusion of the ischemic region caused a return of all diastolic pressures nearly to control values. These observations indicate that coronary extravascular resistance is affected by ischemia and that the most prominent effects are in the subendocardium during systole and in the subepicardium during diastole.