Myocardial Microcirculation Research Articles

Myocardial microcirculation abnormalities and sympathetic nerve dysfunction in patients with diabetes mellitus: A nuclear approach with thallium-201 and iodine-123 MIBG

Myocardial microcirculation abnormalities and sympathetic nerve dysfunction in patients with diabetes mellitus: A nuclear approach with thallium-201 and iodine-123 MIBG

Lipoxygenase inhibitor FLM 5011, an effective protectant of myocardial microvessels against ischemia-reperfusion injury? An ultrastructural-morphometric study

The lipoxygenase inhibitor FLM 5011 was used for protection of the coronary microcirculation against ischemia/ reperfusion injury after ligation of the left coronary artery in dogs. Epimyocardial biopsies from ischemic and non-ischemic areas of protected and unprotected areas taken before and after ischemia of 90 min duration and after 180 min reperfusion were analysed by means of electron microscopic morphometry. The ischemic injury consisted in endothelial swelling, luminal blebbing, and formation of irregular protrusions, partly occurrence of pericapillary edema and cellular debris. Plasmalemmal vesicles seemed to decrease in frequency, mitochondria showed focal or generalized degeneration of cristae and matrix. Reperfusion partly deteriorated the damage, partly restoration of ultrastructural parameters was to be observed. There were no significant differences between the infarcted and not infarcted areas. FLM 5011 treatment reduced the endothelial edema, blebbing and occurrence of pericapillary debris and stabilized the number of vesicles. The protection of the mitochondrial cristae and matrix was statistically significant. The results indicate that FLM 5011, under the condition of the experiment, effectively protects the ultrastructure of essential endothelial structures of myocardial microcirculation, explained by the blocking of the noxious leucotrienes and peptidoleucotrienes liberated by the 5-lipoxygenase pathway of the free arachidonic acid and by scavenging of oxygen free radicals. The results must be confirmed by further experiments including biochemical and functional parameters.

Microbubble persistence in the microcirculation during ischemia/reperfusion and inflammation is caused by integrin- and complement-mediated adherence to activated leukocytes.

Albumin microbubbles that are used for contrast echocardiography persist within the myocardial microcirculation after ischemia/reperfusion (I-R). The mechanism responsible for this phenomenon is unknown. Intravital microscopy of the microcirculation of exteriorized cremaster muscle was performed in 12 wild-type mice during intravenous injections of fluorescein-labeled microbubbles composed of albumin, anionic lipids, or cationic lipids. Injections were performed at baseline and after 30 to 90 minutes of I-R in 8 mice and 2 hours after intrascrotal tumor necrosis factor-alpha (TNF-alpha) in 4 mice. Microbubble adherence at baseline was uncommon (<2/50 high-power fields). After I-R, adherence increased (P<0.05) to 9+/-5 and 5+/-4 per 50 high-power fields for albumin and anionic lipid microbubbles, respectively, due to their attachment to leukocytes adherent to the venular endothelium. TNF-alpha produced even greater microbubble binding, regardless of the microbubble shell composition. The degree of microbubble attachment correlated (r=0.84 to 0.91) with the number of adhered leukocytes. Flow cytometry revealed that microbubbles preferentially attached to activated leukocytes. Albumin microbubble attachment was inhibited by blocking the leukocyte beta(2)-integrin Mac-1, whereas lipid microbubble binding was inhibited when incubations were performed in complement-depleted or heat-inactivated serum rather than control serum. Microvascular attachment of albumin and lipid microbubbles in the setting of I-R and TNF-alpha-induced inflammation is due to their beta(2)-integrin- and complement-mediated binding to activated leukocytes adherent to the venular wall. Thus, microbubble persistence on contrast ultrasonography may be useful for the detection and monitoring of leukocyte adhesion in inflammatory diseases.

Quantitative study of myocardial microcirculation in arterial hypertension due to progressive inhibition of NO synthesis

To study the quantitative changes in intramyocardial blood vessels in rats in whom nitric oxide synthesis was inhibited. Four groups of 10 rats were studied: control (C25 and C40) and L-NAME (L25 and L40). The animals L25 and L40 received L-NAME in the dosage of 50mg/kg/day for 25 and 40 days, respectively. On days 26 and 41 the animals in groups 25 and 40 were sacrificed. Analysis of the myocardium was performed using light microscopy and stereology. Arterial blood pressure and heart weight increased 74.5 and 57.8% after 25 days and 90.2 and 34.6% after 40 days, respectively. Comparing the L-NAME rats with the respective controls revealed that vessel volume density decreased 31.3% after 40 days, and the vessel length-density decreased 53.5% after 25 days and 25.7% after 40 days. The mean cross-sectional area of the vessels showed an important reduction of 154.6% after 25 days. The intramyocardial vessels decreased significantly in length-density in the L-NAME animals. The mean cross-sectional area of the vessels, which normally increases during heart growth between 25 and 40 days, showed a precocious increase by the 25th day in the L-NAME rats. This suggests an increase of the size of the heart, including blood vessels. The inhibition of the NO synthesis provokes rarefaction in the intramyocardial vessels that progresses with the time of administration of L-NAME.

Non-invasive characterization of cardiac microvascular disease by nuclear medicine using single-photon emission tomography.

In about 10 to 30% of patients with typical angina undergoing coronary angiography for suspicion of stenotic coronary artery disease angiographically normal coronary arteries are found. Kemp et al. in 1973 coined the term syndrome X to describe this entity. In a substantial portion of these patients pathologic findings in myocardial scintigraphy are present. Sensitivity and specificity of thallium-201 exercise imaging by visual analysis of images in the presence of significant coronary stenosis is 84 and 88%, respectively. Several investigators have reported abnormal results in radionuclide exercise tests in patients with angiographically normal coronary arteries. Some of these results can be explained by myocardial bridging, vasospasm, left or right bundle branch block, hypertrophic cardiomyopathy, or absorption artifacts. In the majority of cases, however, these abnormalities are not sufficient to explain the scintigraphic findings. Formerly often claimed "false positive", recent studies suggest that endothelial dysfunction might be the reason for the observed perfusion defects. When comparing patients with angiographically unobstructed coronary arteries with and without perfusion defects in stress myocardial perfusion imaging, patients with pathological results show a significantly lower increase of coronary flow after intracoronary injection of the endothelial-dependent vasodilator acetylcholine. Endothelial-independent vasodilation, however, is not impaired in these patients. In addition, intracoronary Doppler measurements reveal that perfusion defects in myocardial scintigraphy only occur if coronary blood flow in this perfusion area is significantly reduced. These results suggest that regional endothelial dysfunction may cause hypoperfusion in myocardial perfusion imaging and underline the important role of the microcirculation in the distribution of radiotracers. Another striking scintigraphic pattern in patients with microvascular angina is the high incidence of reverse redistribution. These perfusion defects, apparent in images obtained 4 hours after exercise stress testing, often cannot be assigned to the perfusion territory of one of the major epicardial vessels. This results in a marked inhomogeneous radionuclide distribution pattern in resting images. The inhomogeneity is associated with a significant reduced resting coronary flow velocity in these patients. As histologically confirmed microvessel disease is often accompanied by slow-flow phenomenon reflecting decreased resting flow velocity, the results suggest that the inhomogeneous perfusion pattern is caused by microvascular dysfunction. Furthermore, the heterogeneity of nuclide distribution supports the hypothesis that endothelial function is not homogeneous in the entire myocardial microcirculation, but varies considerably. In conclusion, microvascular dysfunction by itself seems to cause regional myocardial hypoperfusion, as documented by myocardial scintigraphy. When interpreting pathological scintigraphic results in patients without significant epicardial stenosis, true blood flow and myocardial perfusion abnormalities must be assumed.

MR measurement of coronary blood flow

The functional significance of coronary arterial stenosis can be evaluated by measuring the pharmacological flow reserve. Magnetic resonance (MR) imaging has a unique potential for noninvasive measurement of coronary blood flow and flow reserve in the native coronary artery and bypass graft. Restenosis after coronary balloon angioplasty and stenting in the left anterior descending artery can be detected noninvasively with serial MR measurements of the coronary flow reserve. Further refinement of the MR pulse sequences to improve spatial and temporal resolutions may permit accurate quantification of blood flow volume and flow reserve in all major coronary arterial branches. MR assessments of blood flow volume and flow pattern allow noninvasive detection of significant stenosis in the coronary artery bypass graft as well. By integrating MR blood flow measurement in the coronary sinus and cine MR assessment of left ventricular myocardial mass, altered myocardial micro-circulation in patients with diffuse myocardial diseases, such as hypertrophic cardiomyopathy and cardiac transplant, has been documented. J. Magn. Reson. Imaging 1999;10:728-733.

Measurement of in vivo myocardial microcirculatory function with electron beam CT.

The purpose of this work was to examine the capability of electron beam CT (EBCT) to characterize responses of recruitable (capillaries and small arterioles) compared with nonrecruitable (small to large arterioles) myocardial microvessels to vasoactive substances. Myocardial perfusion (F) and total intramyocardial blood volume (BV) of the anterior cardiac wall were quantitated in 36 pigs, using EBCT and intravenous contrast agent injections, before and after intracoronary administration of either NG-monomethyl-L-arginine (L-NMMA), nitroglycerin, adenosine, or saline. Plotting the relationship of BV and F provided values for the recruitable and nonrecruitable microvascular transit times and BV allotment. Nitroglycerin increased nonrecruitable BV by 84.5+/-7.4%, whereas adenosine increased both recruitable and nonrecruitable microvascular BV (47.1+/-18.9 and 66.0+/-10.9%, respectively). L-NMMA led to a 25.1% decrease only in the recruitable BV. In the control group, no changes were observed. Characteristic responses of different-size myocardial microvessels may be inferred with EBCT, which provides a unique opportunity to portray intramyocardial microcirculatory function noninvasively.

Delayed response of myocardial flow reserve to lipid-lowering therapy with fluvastatin.

Lipid-lowering therapy can improve endothelial function in patients with coronary artery disease (CAD) and hypercholesterolemia. Little is known about induced changes in myocardial microcirculation. This study prospectively investigated the temporal effects of lipid-lowering therapy with fluvastatin on coronary flow and flow reserve (CFR) in patients with CAD assessed by PET. In an open clinical trial, CFR was studied in 15 patients with angiographically documented multivessel CAD and hypercholesterolemia (LDL >160 mg/dL). Dynamic 13N-labeled ammonia PET imaging in conjunction with adenosine was used to assess regional and global CFR at baseline as well as at 2 and 6 months during treatment with fluvastatin (60 to 80 mg/d). Despite a rapid decrease in total cholesterol (29+/-6%) and LDL (37+/-9%), myocardial blood flow at rest and during stress was unchanged after 2 months of treatment (2.7+/-0.9 versus 2.5+/-0.6 mL x g-1 x min-1). At 6 months, stress blood flow as well as CFR increased significantly (3.4+/-1.0 mL x g-1 x min-1). No change in hemodynamic parameters was noted during the entire study. Nine of 15 patients increased CFR by >20%. All responders demonstrated improvement in anginal symptoms, whereas nonresponders stated no change (n=4) or worsening of symptoms (n=2). The improvement in CFR was not related to the amount of lipid lowering and was independent of the severity of stenoses. Improvement in stress blood flow and CFR is delayed compared with the lipid-lowering effect of fluvastatin, suggesting a slow recovery of the vasodilatory response to adenosine.

Myocardial Microcirculation Stereological Changes in Rats Subjected to Nitric Oxide Synthesis Inhibition

This work aims to study stereological changes in intramyocardial blood vessels in rats submitted to nitric oxide (NO) synthesis inhibition within different periods. NO synthesis inhibition was achieved by administration of L-NAME (50 mg/kg/day); control and L-NAME rats were sacrificed 25 and 40 days after experimentation. Light microscopy and stereology [according to references 7, 13 and 14] were used for analyzing the myocardium. Arterial blood pressure and cardiac weight increased by 74.5% and 57.8% after 25 days and by 90.2% and 34.6% after 40 days, respectively. Comparing the L-NAME rats with corresponding controls revealed that the volume density of the vessels decreased by 31.3% after 40 days, and the length density by 53.5% after 25 days and by 25.7% after 40 days. The mean cross-sectional area of the vessels increased by 154.6% after 25 days. In this study on intramyocardial vessels, we observed an important decrease of the length density in L-NAME animals. Likewise, the volume density also decreased significantly in L-NAME animals. The mean cross sectional area of the vessels, which normally increases during cardiac growth between 25 and 40 days, was precociously increased in L-NAME animals at 25 days, suggesting that these animals suffer from a precocious increase of the heart (including blood vessels) due to pressure overload. Stereology of cardiac microvessels revealed remodeling of these vessels in rats under NO synthesis inhibition. Although these changes may be caused by NO inhibition and not by arterial hypertension, further comparative studies on different models of arterial hypertension are needed to confirm this hypothesis.

Inflammatory Alterations in the Myocardial Microcirculation

Inflammatory mechanisms are involved in the pathophysiology of cardiovascular disease and the present review focus us on the association between inflammation and microvascular endothelial dysfunction in the heart, i.e. reduced endothelium-dependent vasodilation of coronary resistance vessels. This abnormality is caused by reduced bioactivity of nitric oxide (NO), and it is found in a variety of conditions, including ischemic heart disease, cardiac allograft vasculopathy, diabetes, hypercholesterolemia, and smoking. At the level of the myocardial microcirculation, reperfusion injury manifests itself as endothelial dysfunction, no-reflow, and increased permeability, which are all probably the result of reperfusion-induced augmentation of the inflammatory response. In other animal models of cardiovascular disease, inflammatory alterations have been described that can contribute to microvascular endothelial dysfunction and reactive oxygen species, neutrophils, tumour necrosis factor-α, and inducible NO synthase are among the mediators that have been incriminated. Circulating levels of inflammatory mediators may serve as molecular markers of cardiovascular disease, and antiinflammatory interventions hold some promise for future cardiovascular therapy.

Temporospatial heterogeneity of myocardial perfusion and blood volume in the porcine heart wall.

Spatial heterogeneity of myocardial perfusion has been recognized for many years. Whether this is primarily the result of heterogeneity of parameters such as myocardial metabolism, of intramyocardial mechanical forces, or of vasomotor function within the myocardial microcirculation, is not clear. A practical problem is that it has been almost impossible to measure any two of these parameters simultaneously in the same piece of myocardium so that an unambiguous correlation, much less a cause-and-effect relationship, has been difficult to establish. In this study of six anesthetized pigs, we propose that whole-body computed tomography is a method for providing the simultaneous measurement of heterogeneity of myocardial perfusion (F) and myocardial blood volume (rho). The first finding was that the empirical relationship rho=AF+BF(0.5) between myocardial blood flow (F) and intramyocardial blood volume (rho) is maintained over a range of sizes of regions of interest (approximately 1 to 0.125 cm3) within the myocardium of each individual animal despite the spatial heterogeneity of the F and the rho values. The value of A ranges from 0.014 to 0.021 min and of B ranges from 0.061 to 0.076 ml(0.5) g(-0.5) min(0.5). A second finding was that the pattern of spatial heterogeneity of F and of rho remained reasonably stable over at least a 1 h period.

Endothelin-1 myocardial clearance, production, and effect on capillary permeability in vivo.

Myocardial metabolism of endothelin-1 (ET-1) and its effect on coronary microcirculatory exchanges were obtained in anesthetized dogs by combining the indicator-dilution technique with immunoreactive ET-1 measurements. The myocardium extracted 17.7 +/- 4.6% of tracer ET-1 (n = 12). Simultaneously measured ET-1 levels in the aorta (0.97 +/- 0.46 pg/ml) and coronary sinus (0.96 +/- 0.53 pg/ml) were not different, supporting a production of ET-1 by the heart that balances the amount extracted. Intracoronary infusion of ET-1 (5 ng.kg-1.min-1) increased coronary sinus ET-1 levels approximately 50-fold, decreased coronary blood flow per unit of interstitial space by approximately 30% (P = 0.006), and increased myocardial microcirculatory transit times (n = 6). Permeability to albumin was unaffected by ET-1, whereas the permeability-surface area product for sucrose decreased following derecruitment of myocardial capillaries. We conclude that there is a normal myocardial metabolic balance of ET-1 and that the heart marginally contributes to circulating ET-1. Pharmacological doses of ET-1 may adversely affect myocardial metabolism by reducing blood flow and the permeability-surface area product for small circulating substances.

Red cell flux during the cardiac cycle in the rabbit myocardial microcirculation.

(1) To measure regional phasic myocardial red cell flux during a cardiac cycle using a laser Doppler velocimeter. (2) To test the responses of regional red cell flux to a vasodilator (adenosine), a vasoconstrictor (angiotensin II), and an inotrope (isoproterenol). Using an anaesthetised open-chest rabbit with the pericardium intact a 140-micron-tip fibre optic probe was placed in the left ventricular myocardium in various locations. With the fibre in place drugs were given to alter myocardial loading conditions while red cell flux was registered. Phasic red cell flux was similar in the epicardium to endocardium giving an average endo/epi ratio of 1.14 in the rabbit heart. At least two peaks of increased red cell flux within a single cardiac cycle were observed. Some unique patterns for red cell flux were observed in specialised myocardial structures. Adenosine increased red cell flux but minimally changed the pattern of phasic flux throughout the cycle. Laser Doppler velocimetry permits the recording of phasic red cell flux during the cardiac cycle in the myocardial microcirculation. Its pattern is determined by both coronary arterial inflow and venous outflow. The pattern of red cell flux may be characteristic for a region-probably determined by difference in tissue pressure (attributable to the pattern of muscle fibre shortening and collagen tethering) and changes in capillary length and density.

Quantitative evaluation of regional myocardial perfusion using fast X-ray computed tomography.

Clinical quantitation of regional myocardial perfusion using a minimally invasive and easily applied technique could allow for ready quantitation of the functional significance of coronary disease, allow for further understanding of flow reserve in various cardiomyopathic and hemodynamic overload (pressure versus volume) conditions, and possibly provide basic information needed regarding the development and clinical significance of coronary collateral vessels and diseases of the myocardial microcirculation. Electron beam CT (EBCT) is a unique cardiac imaging modality that allows for rapid acquisition tomographic slices of the heart with excellent spatial resolution. It has been demonstrated to provide accurate measurements of cardiac anatomy, biventricular function, myocardial mass, and estimates of mural atherosclerotic plaque burden via quantification of coronary calcium. The application of classical indicator techniques for use by fast x-ray computed tomography techniques such as electron beam CT has been shown to allow quantitative analysis of regional myocardial perfusion throughout the myocardium. Initial studies using central intravenous contrast injection in experimental animals showed a close correlation of regional myocardial perfusion as quantitated by electron beam CT with measurements using radiolabeled microspheres at resting and moderately increased flow states. At high flow states, however, electron beam CT significantly underestimated absolute myocardial perfusion and thus myocardial flow reserve. Using another fast CT device, the Dynamic Spatial Reconstructor (DSR), concepts of intramyocardial vascular blood volume and its relation to myocardial flow have been established. By adapting these concepts to electron beam CT scanning and accounting for the increase in intramyocardial vascular blood volume at vasodilatation, the ability to correctly quantitate perfusion states up to approximately 400 mL.min-1. 100 g-1 using central intravenous contrast administration was demonstrated. This implies that studies can be done with intravenous injection methods for characterization of regional myocardial perfusion up to the normal flow reserve of approximately 4:1. Important physiologic and clinical abnormalities in flow reserve generally result in a ratio < 3:1. Electron beam CT offers the capability to quantitate regional myocardial perfusion in both the clinical and research setting. Of particular interest is the ability to provide quantitative regional myocardial perfusion which can be coupled to the evaluation of cardiac anatomy and function as well as mural coronary atherosclerotic calcium burden during the same scanning session. Thus, electron beam CT has the potential to become a valuable, minimally invasive clinical tool for comprehensive analysis of cardiac function and coronary status.

Pathogenesis of chronic Chagas' myocarditis: An overview

The evidence provided by both human and animal studies on chronic Chagas' heart disease suggests that the development of the chronic fibrosing myocarditis is related to progressive and additive focal cellular necrosis with associated inflammatory lymphomononuclear infiltrate, reactive and reparative myocardial fibrosis, surrounding myocyte hypertrophy. These processes may be initiated and perpetuated by alterations in the myocardial microcirculation and by autoimmune factors. These findings could foster future therapeutic strategies in the management of chronic chagasic patients to optimize the medical treatment and hopefully to improve prognosis.

Coronary Microcirculation During Left Heart Bypass with a Centrifugal Pump.

To estimate coronary microcirculation during left heart bypass (LHB), we performed an experimental comparison study of LHB and intraaortic balloon pumping (1ABP). LHB was performed with a BioMedicus BP-80 pump supporting half of the flow of cardiac output whereas the IABP was pumped in a 1:1 mode for cardiogenic shock in a swine model. Coronary circulations were analyzed by electromagnetic flowmeter, pulsed Doppler velocimeter, and laser Doppler flowmeter. Left ventricular end-diastolic pressure (LVEDP) was reduced significantly by LHB. Although there was no significant difference in epicardial flow between the LHB and IABP groups, endocardial flow was increased significantly by LHB. In the LHB group, the systolic reverse wave of the coronary velocity called a myocardial invalid circulation was reduced remarkably. There was a significant inverse correlation between endocardial flow and LVEDP. These results suggested that LHB was more effective for myocardial microcirculation than was IABP.

Coronary flow velocity immediately after reperfusion reflects myocardial microcirculation in canine acute myocardial infarction models

Coronary flow velocity immediately after reperfusion reflects myocardial microcirculation in canine acute myocardial infarction models

Cardiomyopathy in rats with Walker 256 tumor: The potential role of microvascular disease in its genesis

Considering that diffuse abnormalities of myocardial microcirculation with transient ischemia have been suggested to play a role in the genesis of myocytolytic necrosis, characteristic lesion of dilated or congestive cardiomyopathies, and the bloodstream is the most common pathway for dissemination of cancer cells, which gain access to the microcirculation, the present study was undertaken to search for morphologic and electrocardiographic evidence of myocardial damage associated with microcirculatory disease in rats experimentally inoculated with the Walker 256 tumor. Young albino rats inoculated intramuscularly with the Walker 256 tumor developed a cardiomyopathy characterized by diffuse small foci of myocytolytic necrosis, decreased thickness of the mean left midventricular wall associated with reduced size of the minor diameter of myocytes, and electrocardiographic abnormalities reflecting the myocardial damage, correlated with the presence of a microvascular disease, characterized by intramyocardial microvessels (less than 50 μm in diameter) partially or totally occluded because of entrapment of tumor cells and fibrin-platelet/tumor cell-cellular debris thrombi. The occlusive or subocclusive small vessel lesions preceded the development of the myocytolytic necrosis, suggesting that the microvascular disease would play an important role in the process of focal micronecrosis and consequent electrocardiographic changes. However, it must be taken into account that the tumor thromboemboli can generate related factors that could promote cell injury and cell death. In conclusion, the hematogenic dissemination of Walker 256 cells promotes the development of an experimental cardiomyopathy attributable, at least in part, to microvascular obliterative changes in the myocardium.

A pathogenic mechanism of chronic ongoing myocarditis.

To clarify the pathogenetic mechanism of chronic ongoing myocarditis, we produced Coxsackievirus B3-induced myocarditis in A/J mice and immunopathologically examined the microcirculation in the chronic phase of myocarditis. Forty-two 3-week-old A/J mice were inoculated intraperitoneally with Coxsackievirus B3 (Nancy strain) 2 x 10(4) PFU (plaque-forming units) and sacrificed 7, 14, 21, 50, 90, or 120 days later. To evaluate myocardial microcirculation, 18 of the hearts were perfused from the thoracic aorta with warm 2% gelatin/carbon solution. The remaining hearts were quickly frozen for immunologic analysis with an enzyme immunostaining assay using monoclonal antibodies against CD4, CD8, macrophages, intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex class I or II. The presence of viral RNA genome in the myocardium at 40, 50, or 60 days after inoculation was evaluated using the polymerase chain reaction. The lesions in chronic ongoing myocarditis consisted of myocardial damage, myocardial calcification, interstitial fibrosis, and infiltration of mononuclear cells. These infiltrated lymphocytes were predominantly CD4+ T cells. Furthermore, microvascular abnormalities, including dilatation, tortuosity, constriction, and abrupt termination, were observed around the lesions. There was marked infiltration by mononuclear cells around the microvessels. ICAM-1 was strongly expressed in the endothelial cells of the vessels. Coxsackie B3 viral genome was not detected in the myocardium of mice with chronic ongoing myocarditis in each stage examined. These results suggest that an autoimmune mechanism is involved in the persistent inflammation seen in chronic ongoing myocarditis.

Computed tomography evaluation of regional increases in microvascular permeability after reperfusion of locally ischemic myocardium in intact pigs

I evaluated how well fast computed tomography (CT) scanning could quantify altered myocardial microvascular function resulting from transient ischemia and subsequent reperfusion. A major epicardial coronary artery of anesthetized pigs was occluded for either 0, 15, 30, 60, or 120 min. Fast X-ray CT scan sequences were performed before and during occlusion and 30, 60, and 90 min after onset of subsequent reperfusion. Regional myocardial perfusion, intramyocardial blood volume, and myocardial microcirculatory permeability-surface area product were estimated from the CT scan sequences. With the increasing duration of ischemia, the permeability-surface area product remained unchanged during reperfusion (p > .05), but an index of myocardial microvascular permeability increased with the progressive duration of ischemia and of reperfusion (p < .05). These CT-based findings are consistent with published, more invasive demonstrations that capillary permeability is increased during postischemic reperfusion in proportion to the duration of the preceding ischemia.