Cardiorespiratory Fitness and Coronary Artery Calcification in a Primary Prevention Population.

OBJECTIVE: To elucidate whether cardiorespiratory fitness (CRF) is protective or contributory to coronary artery disease plaque burden. PATIENTS AND METHODS: Study participants were working middle-aged men from the Mayo Clinic Executive Health Program who underwent coronary artery calcium (CAC) assessment and exercise treadmill testing for risk stratification. Data from January 1, 1995, through December 31, 2008, were considered. The CAC assessment score was used for lifelong plaque burden analysis; functional aerobic capacity (FAC) from treadmill testing was analyzed as 4 ranked categories of CRF. Known risk factors for cardiovascular disease, including family history, were also considered. RESULTS: In 2946 male patients in this retrospective, cross-sectional, observational study, known cardiovascular risk factor profiles and risk calculations tended to uniformly improve with increasing CRF, defined by the FAC level. Only the above-average group, or the third of 4 levels, was found consistently lower than other levels of FAC for CAC scores. The above-average group also had statistical significance after controlling for age, body mass index, and family history of coronary artery disease in a U-shaped distribution rather than the expected linear dose-response relationship. Plaque burden was significantly increased in patients with the highest FAC level (P=.005) compared with the above-average group despite the observed maximal risk factor optimization in all known conventional cardiovascular risk factors. CONCLUSION: For men, maximal CRF is associated with increased atherosclerosis, established with CAC scores. By comparison, average-to-moderate CRF appears to be cardioprotective regardless of either age or the influence of other contributing, recognized cardiac risk factors.

Coronary microcirculation changes in non-ischemic dilated cardiomyopathy identified by novel perfusion CT.

Intramyocardial microvessels demonstrate functional changes in cardiomyopathies. However, clinical computed tomography (CT) does not have adequate spatial resolution to assess the microvessels. Our hypothesis is that these functional changes manifest as altered heterogeneity of the spatial distribution of arteriolar perfusion territories. Our goal was to determine whether the spatial analysis of perfusion CT could clinically detect changes in the function and structure of the intramyocardial microcirculation in a non-ischemic dilated cardiomyopathy (DCM). Two groups were studied: (1) a Control group (12 male plus 12 female) with no risk factors nor evidence of coronary artery disease, and (2) a DCM group (12 male plus 12 female) with left ventricular ejection fraction ≤40% and no evidence of coronary artery disease. Using the CT scan, the LV free wall thickness and its radius of curvature were measured. The DCM group was sub divided into those with LV free wall thickness <11.5 mm and those with thickness ≥11.5 mm. In the myocardial opacification phase of the CT scan sequence, myocardial perfusion (F) and intramyocardial blood volume (Bv) for multiple intramyocardial regions were computed. No significant differences between the groups were demonstrable in overall myocardial F or Bv. However, the myocardial regional data showed significantly increased spatial heterogeneity in the DCM group when compared to the Control group. The findings demonstrate that altered function of the subresolution intramyocardial microcirculation can be quantified with myocardial perfusion CT and that significant changes in these parameters occur in the DCM subjects with LV wall thickness greater than 11.5 mm.

Diagnostic capability of comprehensive handheld vs transthoracic echocardiography.

OBJECTIVE: To assess the diagnostic capability of handheld echocardiography (HHE) compared with transthoracic echocardiography (TTE) performed and evaluated by experienced sonographers and expert echocardiographers. PATIENTS AND METHODS: We conducted a prospective study of adult outpatients undergoing comprehensive TTE between July 9, 2012, and April 3, 2013. Experienced sonographers performed a detailed, standardized examination using a handheld ultrasound device that included 2-dimensional and color Doppler images from standard imaging windows. Images from TTE and HHE were independently interpreted by expert echocardiographers to whom the other study was masked. Agreement between the standard TTE and the HHE reports was analyzed. RESULTS: The study group contained 190 patients (mean ± SD age, 62 ± 17 years; 49% male [n=93]). The κ values were 0.52 for left ventricular (LV) enlargement, 0.52 for right ventricular enlargement, 0.62 for regional wall motion abnormalities, 0.73 for aortic stenosis, and 0.61 for mitral regurgitation. Lin concordance correlation coefficients ranged from 0.89 for LV end-systolic diameter to 0.78 for LV end-diastolic diameter. In 51 patients (27%), echocardiographic findings were discordant between HHE and standard TTE. The most common discordant finding was the presence vs absence of any regional wall motion abnormalities. In discordant cases, HHE tended to underestimate, rather than overestimate, the severity of abnormal findings. CONCLUSION: In experienced hands, HHE shows moderate correlation with standard TTE, but discordant findings were present in 27% of patients. Even when performed and interpreted by experienced operators, HHE should not be used as a surrogate for standard TTE. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01558518.

Early changes in myocardial microcirculation in asymptomatic hypercholesterolemic subjects: as detected by perfusion CT.

Intramyocardial microvessels show functional changes in early stages of atherosclerosis prior to epicardial coronary artery stenosis. However, clinical CT does not have adequate spatial resolution to resolve the microvessels. To clinically detect changes in the function of the intramyocardial microcirculation, the spatial heterogeneity of the distribution of myocardial perfusion (F) and intramyocardial microcirculatory blood volume (Bv) was determined by perfusion CT. Two human subject groups were studied: (i) a "Control" group (24) with no risk factors nor evidence of coronary artery disease (CAD), and (ii) an "At-Risk" group (24) with hypercholesterolemia, but no evidence of CAD. In the perfusion CT image, a region of interest (ROI) covering the left ventricular myocardium was subdivided into multiple nested ROI (nROI) of equal size and used to compute F and Bv for each nROI. No significant differences between the groups were demonstrable in overall myocardial F, or Bv. The nROI data showed significantly increased spatial heterogeneity in the "At Risk" group when compared to "Control" subjects. This study demonstrates that subresolution distribution at the microcirculatory level can be quantified with myocardial perfusion CT and significant changes in these parameters occur in hypercholesterolemic subjects before they have developed significant changes in conventional perfusion parameters.

Self-rated stress is noncontributory to coronary artery disease in higher socioeconomic strata.

Stress and its attendant psychosocial and lifestyle variables have been associated with coronary artery disease (CAD), yet the contribution of socioeconomic status (SES) has not been addressed. The aim of this study is to determine if stress assessment is associated with CAD independent of SES, and is incremental to the Framingham Score. The study group consisted of 325 executive patients undergoing comprehensive health assessment. Stress was assessed utilizing the validated "Self-Rated Stress" (SRS) instrument. Coronary artery calcification (CAC) served to assess the degree of atherosclerosis, a CAD equivalent and risk assessment tool. The relationship between SRS and CAC was assessed, with adjustment by potential confounders. CAC was modeled by a variety of cut points (>0, ≥5, ≥100, ≥200) for the test of trend across stress levels per Mantel-Haenszel chi-square (1 df) with nonsignificant P values of 0.9960, 0.5242, 0.1692, 0.3233, respectively. A logistic regression model with SRS as a categorically ranked and continuous variable to predict binary outcome of calcification yielded P values of 0.2366 and 0.9644; this relationship, further adjusted by age, fruit and vegetable consumption, exercise, and education, yielded no statistically significant association. No improvement of fit was observed for the established Framingham Score to CAC relation utilizing SRS. The study concluded that SRS did not play a role in early CAD when focusing on a population in higher socioeconomic strata, and SRS did not add predictive value beyond patient age or calculated Framingham risk. Future studies should focus on additional validated instruments of stress to differentiate between subtypes of stress for varying SES strata.

Outcomes in patients with chest pain evaluated in a chest pain unit: the chest pain evaluation in the emergency room study cohort.

BACKGROUND: Limited data exist on the long-term outcomes of patients who undergo evaluation in a chest pain unit (CPU). METHODS: Our study included patients with chest pain at intermediate risk for acute cardiovascular events enrolled in the CHEER study. The primary outcome included a composite of death, myocardial infarction, acute heart failure, stroke, and out-of-hospital cardiac arrest. The secondary outcome included a composite of cardiovascular death, myocardial infarction, acute heart failure, stroke, revascularization, and unstable angina. Data were obtained through a medical record review. We compared outcomes between groups randomized to the CPU versus admission, those admitted from the CPU versus dismissed home, and those who were admitted versus dismissed home after a cardiac stress test in the emergency department. RESULTS: The final analysis included 407 patients. Median surveillance length was 5.5 years. No differences in the primary outcome or secondary outcome existed between patients randomized to the CPU versus admitted to hospital (21.6% vs 20.2% and 29.9% vs 33.0%, respectively, P > .05 for all comparisons). Patients admitted from the CPU had higher rates of the secondary outcome (adjusted hazard ratio 2.26) than patients dismissed from the CPU. Patients admitted after a cardiac stress test in the CPU had higher rates of the secondary outcome (adjusted hazard ratio 2.42) than patients dismissed from the CPU. CONCLUSIONS: A CPU does not increase long-term adverse outcomes in patients with chest pain at intermediate risk for an acute event.

Computed tomographic coronary artery calcium assessment for evaluating chest pain in the emergency department: long-term outcome of a prospective blind study.

OBJECTIVE: To determine the long-term outcome of computed tomographic (CT) quantification of coronary artery calcium (CAC) used as a triage tool for patients presenting with chest pain to an emergency department (ED). PATIENTS AND METHODS: Patients (men aged 30-62 years and women aged 30-65 years) with chest pain and low-to-moderate probability of coronary artery disease underwent both conventional ED chest pain evaluation and CT CAC assessment prospectively. Patients' physicians were blinded to the CAC results. The results of the conventional evaluation were compared with CAC findings on CT, and the long-term outcome in patients undergoing CT CAC assessment was established. Primary end points (acute coronary syndrome, death, fatal or nonfatal non-ST-segment elevation myocardial infarction, fatal or nonfatal ST-segment elevation myocardial infarction) and secondary outcomes (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, coronary stenting, or a combination thereof) were obtained when the patient was dismissed from the ED or hospital and then at 30 days, 1 year, and 5 years. RESULTS: Of the 263 study patients, 133 (51%) had a CAC score of zero. This absence of CAC correlated strongly with the likelihood of noncardiac chest pain. Among 133 patients with a CAC score of zero, only 1 (<1%) had cardiac chest pain. Conversely, of the 31 patients shown to have cardiac chest pain, 30 (97%) had evidence of CAC on CT. When a CAC cutoff score of 36 was used, as suggested by receiver operating characteristic analysis, sensitivity was 90%; specificity, 85%; positive predictive value, 44%; and negative predictive value, 99%. During long-term follow-up, patients without CAC experienced no cardiac events at 30 days, 1 year, and 5 years. CONCLUSION: Findings suggest that CT CAC assessment is a powerful adjunct in chest pain evaluation for the population at low-to-intermediate risk. Absent or minimal CAC in this population makes cardiac chest pain extremely unlikely. The absence of CAC suggests an excellent long-term (5-year) prognosis, with no primary or secondary cardiac outcomes occurring in study patients at 5-year follow-up.

Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women.

While the risk for symptomatic atherosclerotic disease increases after menopause, currently recognized risk factors do not identify ongoing disease processes in low-risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by the Framingham risk score. The concentration and phenotype of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry, and coronary artery calcification (CAC) was scored using 64-slice computed tomography scanners. The procoagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, serum lipids, systolic blood pressure (Framingham risk score < 10%, range 1-3%), and high-sensitivity C-reactive protein did not differ significantly among women with low (0 < 35; range, 0.3-32 Agatston units) or high (>50; range, 93-315 Agatston units) CAC compared with women without calcification. The total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. The thrombin-generating capacity of the isolated microparticles correlated with phosphatidylserine expression, which also was greatest in women with high CAC scores. The percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, the characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis.

Pilot study of sex differences in chemokine/cytokine markers of atherosclerosis in humans.

BACKGROUND: Atherogenic processes increase in women after menopause, when the risk of cardiovascular adverse events approaches that observed in age-matched men. In experimental animals, ovariectomy increases the platelet content of mitogenic cytokines, such as platelet-derived growth factor (PDGF), which when released into the blood or site of vascular injury, contribute to atherogenic processes. OBJECTIVE: Experiments were designed to assess the sex distribution of inflammatorychemokines/cytokines, which may be released from platelets in the serum of middle-aged women and men in whom the extent of atherosclerotic coronary disease was defined by coronary arterial calcification (CAC). METHODS: Blood was obtained from healthy white individuals recruited from the Mayo Clinic database. CAC was assessed by 64-slice computed tomography. Plasma cholesterol, lipids, and high-sensitivity C-reactive protein were analyzed by the Mayo Clinic Department of Laboratory Medicine and Pathology. Serum cytokines were determined using cytokine arrays. Cytokine expression was measured using dot blot analysis. RESULTS: Of the 16 individuals (11 women, 5 men) who agreed to participate in the study, 1 woman was premenopausal, 1 was taking oral contraceptives, and 1 was receiving menopausal hormone therapy. One woman had an active infection and was eliminated from the study. CAC was detected in only 2 of the 11 women (scores of 46 and 56 Agatston units [AU]) but in 3 of the 5 men (scores of 3, 123, and 609 AU). Correcting for all other risk factors, expression of the chemokine RANTES (regulated on activation, normal, T-cell expressed and secreted; CCL5 [CC chemokine ligand 5]) was 100.98% greater in women than in men, and PDGF-BB was 55.30% greater in women than in men. CONCLUSIONS: This small pilot study found that the circulating chemokines/cytokines RANTES and PDGF-BB showed sex-disparate distribution between the women and men studied, and did not appear related to the degree of CAC.

Independent association between obstructive sleep apnea and subclinical coronary artery disease.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with coronary risk factors, but it is unknown if OSA is associated with development of coronary disease. We evaluated the association between OSA and the presence of subclinical coronary disease assessed by coronary artery calcification (CAC). METHODS: Consecutive patients with no history of coronary disease who underwent electron-beam CT within 3 years of polysomnography between March 1991 and December 2003 were included. OSA was defined by an apnea-hypopnea index (AHI) > or = 5 events per hour, and patients were grouped by quartiles of AHI severity. Logistic regression modeled the association between OSA severity and presence of CAC. RESULTS: There were 202 patients (70% male; median age, 50 years; mean body mass index, 32 kg/m(2); 8% diabetic; 9% current smokers; 60% hypercholesterolemic; and 47% hypertensive). OSA was present in 76%. CAC was present in 67% of OSA patients and 31% of non-OSA patients (p < 0.001). Median CAC scores (Agatston units) were 9 in OSA patients and 0 in non-OSA patients (p < 0.001). Median CAC score was higher as OSA severity increased (p for trend by AHI quartile < 0.001). With multivariate adjustment, the odds ratio for CAC increased with OSA severity. Using the first AHI quartile as reference, the adjusted odds ratios for the second, third, and fourth quartiles were 2.1 (p = 0.12), 2.4 (p = 0.06), and 3.3 (p = 0.03), respectively. CONCLUSIONS: In patients without clinical coronary disease, the presence and severity of OSA is independently associated with the presence and extent of CAC. OSA identifies patients at risk for coronary disease and may represent a highly prevalent modifiable risk factor.

Secondary hypertension: current diagnosis and treatment.

Secondary hypertension affects a small but significant number of the hypertensive population and, unlike primary hypertension, is a potentially curable condition. The determinant for workup is dependent on the index of suspicion elicited during patient examination and treatment. Specific testing is available and must be balanced depending on the risk and cost of the workup and treatment with the benefits obtained if the secondary cause is eliminated. This article reviews common manifestations, workup, and the current treatments of the common causes of secondary hypertension.

Benzocaine-induced methemoglobinemia based on the Mayo Clinic experience from 28 478 transesophageal echocardiograms: incidence, outcomes, and predisposing factors.

BACKGROUND: The potentially life-threatening condition of methemoglobinemia is characterized by cyanosis, low pulse oximetric readings, and normal arterial Po(2) values. Acquired methemoglobinemia has been linked to the use of the topical anesthetic benzocaine in endoscopic procedures, including transesophageal echocardiography (TEE). Yet, the incidence of benzocaine-induced methemoglobinemia with TEE and the clinical factors associated with its development are unclear. METHODS: All cases of methemoglobinemia complicating TEE at our institution (from January 1, 1999, to July 1, 2006) were identified by a comprehensive review of medical records and echocardiography and pharmacy databases. RESULTS: During 90 months among 28 478 TEEs, 19 cases of methemoglobinemia were identified, with a mean +/- SD methemoglobin level of 32% +/- 15%. All patients were cyanotic, with low oxygen saturations. Eighteen of 19 patients received methylene blue (mean +/- SD dose, 1.3 +/- 0.4 mg/kg of body weight), with resolution of symptoms and signs. One of 19 cases resolved spontaneously. Compared with a random sample of 190 patients undergoing TEE, the age, sex, body mass index, left ventricular systolic function, and dose of sedation (midazolam hydrochloride, fentanyl citrate, or both) were similar in the 2 groups. However, study patients who developed methemoglobinemia were more likely to be hospitalized (89.5% vs 57.6%, P =.005), be anemic (84.2% vs 44.7%, P =.002), and have active systemic infection (68.4% vs 6.8%; P < .001) at the time of TEE compared with the random control cohort. CONCLUSIONS: In a large series of patients undergoing TEE, the incidence of methemoglobinemia is low (1 case per 1499 [0.067%; 95% confidence interval, 0.040%-0.100%]) and has a good outcome if promptly recognized and treated. Clinical factors associated with the development of methemoglobinemia include sepsis, anemia, and hospitalization. Minimizing or avoiding the use of benzocaine in these patients is recommended.

Left atrial remodelling in mitral regurgitation--methodologic approach, physiological determinants, and outcome implications: a prospective quantitative Doppler-echocardiographic and electron beam-computed tomographic study.

AIMS: To define accurate and normal range of echocardiographic left atrial (LA) volume measurement and to assess the prevalence, determinants, and outcome implications of LA enlargement in mitral regurgitation (MR). METHODS AND RESULTS: We prospectively compared LA volume obtained simultaneously by electron beam-computed tomography (EBCT) and by four echocardiographic methods in 33 test patients. Accurate echocardiographic LA volume measurements were obtained only by biplane area-length method with vertical longitudinal-length (r = 0.95, P < 0.0001; 145 +/- 57 vs. 143 +/- 55 mL, P = 0.57). Using this method, the normal range in 100 normal subjects, the physiological determinants and outcome implications of LA enlargement in 320 patients with organic MR were analysed. In normal subjects, indexed to body surface area, LA index (27 +/- 6 mL/m(2)) was not influenced by age or gender and values > or = 40 mL/m(2) were beyond the upper limit of normal. In MR, the most powerful determinants of LA enlargement were higher regurgitant volume (RVol) and atrial fibrillation (AF) (P < 0.0001), followed by older age, female gender, higher left ventricular end-systolic volume, and mass (all P < 0.001). After diagnosis in sinus rhythm, LA index > or = 40 mL/m(2) predicted superiorly and independently to LA diameter the occurrence of AF [adjusted RR 1.48 (1.06-2.16), P < 0.01] and the combined endpoint of death or need for mitral surgery [adjusted RR 1.61 (1.3-2.0), P < 0.0001]. CONCLUSION: LA remodelling can be accurately assessed by echocardiography and LA index > or = 40 mL/m(2) is beyond the normal range. In organic MR, higher LA index is the combined result of multiple physiological effects, provides independent prognostic information, and therefore should be part of a comprehensive echocardiographic examination.

Assessment of cardiovascular risk status at CT colonography.

PURPOSE: To retrospectively determine whether calcium scores of the abdominal aorta obtained during computed tomographic (CT) colonography relate to Framingham risk factors and clinical cardiac events. MATERIALS AND METHODS: The institutional review board approved the current HIPAA-compliant retrospective study and waived informed consent. Between 1995 and 1998, 480 patients underwent CT colonography; 467 patients were available for assessment. Calcium scores with a threshold attenuation value of 130 HU or greater were recorded for abdominal aorta (suprarenal, infrarenal, and aortic bifurcation regions and total). Patient histories were abstracted for established cardiac risk factors and subsequent cardiac events. Associations between calcium measurements and binary risk factors were assessed with Wilcoxon rank sum test; those with continuous risk factors, with Spearman rank correlation coefficient; and those with combined end points, with Cox proportional hazards model. RESULTS: Follow-up data were available for 467 patients with median age of 65 years (range, 34-83 years); 59% (275 of 467) were men. Nine patients had cardiac events subsequent to CT colonography. Results of proportional hazards regression analysis revealed a significant association between myocardial infarction or cardiac event-related death and calcium scores of the aortic bifurcation that exceeded 895, the value for the 75th percentile for this calcium variable (P < .01). Associations with established cardiac risk factors for all four calcium scores were significant (P < .05). Spearman rank correlation coefficients for associations between total calcium score and patient characteristics of age, number of pack-years of smoking, and systolic blood pressure were 0.51, 0.43, and 0.29, respectively (P < .001 for all). CONCLUSION: Aortic calcification scores at CT colonography are significantly associated with established cardiac risk factors and cardiac-related events. This screening information can be obtained without additional scanning or risk to the patient.

Biphasic Doppler pattern of the descending thoracic aorta: a new echocardiographic finding in patients with aortic valve stenosis.

A total of 59 patients (> or = 65 years of age) with normal left ventricular function (ejection fraction > 50%) and varying degrees of aortic valve structure and hemodynamics (normal to severely stenotic) were screened; 50 were subsequently enrolled. Continuous wave Doppler echocardiography in the descending thoracic aorta showed two general patterns: (1) in aortic stenosis, the pattern consisted of two peak systolic velocity components (S1 and S2); and (2) in normal aortic valve function, the pattern was a uniphasic signal with a single peak systolic velocity component. The new Doppler pattern yielded 95% sensitivity and 90% specificity in the detection of clinically significant aortic valve stenosis, and 92% sensitivity and 70% specificity in the detection of severe aortic valve stenosis. Sensitivity was 96% in uniphasic signals during normal aortic valve function by conventional 2-dimensional and Doppler criteria. This article introduces characteristics of this Doppler velocity profile as a new diagnostic finding of aortic valve stenosis.

Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a common endocrine disorder of reproductive-aged women, is associated with multiple risk factors for coronary heart disease (CHD), such as diabetes mellitus, dyslipidemia, visceral obesity, and hypertension. However, premature coronary atherosclerosis has not been demonstrated in PCOS women. Electron beam computed tomography (EBCT) noninvasively measures coronary artery calcium (CAC), a marker for coronary atherosclerosis. We measured CAC by EBCT in 30- to 45-yr-old premenopausal PCOS women and compared the results to CAC in 1) recruited normal ovulatory volunteers matched for age and weight to the PCOS cohort, and 2) community-dwelling women of similar age in an extant coronary calcium database. Healthy, community-dwelling, ovulatory controls (n = 71) were matched by age and body mass index (BMI) to PCOS women (n = 36). Women with diabetes or known CHD were excluded. Subjects underwent EBCT scanning, oral glucose tolerance testing, and CHD risk factor assessment. PCOS women had significantly higher levels of serum total and low density lipoprotein cholesterol and testosterone levels than matched controls. PCOS and control women were obese and had a greater mean BMI than community-dwelling women (33 kg/m(2) for PCOS vs. 31 kg/m(2) for control; P < 0.001). CAC was more prevalent in PCOS women (39%) than in matched controls (21%; odds ratio, 2.4; P = 0.05) or community-dwelling women (9.9%; odds ratio, 5.9; P < 0.001). BMI, waist circumference, and total and low density lipoprotein cholesterol levels predicted CAC prevalence after adjustment for BMI. CAC is more prevalent in PCOS women than in obese or nonobese women of similar age. PCOS women are at increased risk for atherosclerosis and should be targeted for primary prevention of CHD.

Intramyocardial blood volume, perfusion and transit time in response to embolization of different sized microvessels.

OBJECTIVE: To study the role of the coronary microcirculation in response to different-sized microemboli, we measured changes in intramyocardial microvascular blood volume (Bv), perfusion (F) and transit time (TT) and also microvascular patterns of injury. METHODS: Bv, F and TT were quantitated in 24 pigs at baseline and again 2 min after repeat injections of 10- or 100-microm microspheres at rest or during intracoronary adenosine infusion. The association of Bv and TT was assessed in the microsphere pigs and in nine control pigs. Microvascular injury was studied on gross-pathologic and histologic samples. RESULTS: At rest, initial injection of 10-microm microspheres led to increases in Bv and F, but progressively decreased with additional injections. In contrast, even small numbers of 100-microm microspheres always led to decreases in Bv and F. Injection of microspheres during adenosine-induced vasodilation always resulted in decreases in peak Bv and F irrespective of their diameters, but microvascular TTs remained unaltered. In control pigs, however, TTs were inversely related to adenosine-induced changes in Bv. Histologically, 100-microm microspheres resulted in patchy distribution of microcirculatory plugging, while 10-microm microspheres induced contiguous hemorrhagic myocardial injury. CONCLUSION: Microsphere-induced changes in intramyocardial Bv and F and the associated pattern of myocardial injury are related to the size of embolized microvessels and the initial perfusion state. Microvascular functional volume reserve mechanisms appear to play a key role accompanying flow- and TT-preservation.

Three-Dimensional Imaging Used for Virtual Dissection, Image Banking and Physical Replication of Anatomy and Physiology.

Historically, techniques of dissection have been used to aid in our understanding of human anatomy, physiology, and pathology. However, these techniques alter the structures and fine details being studied. New advances in computer technology, imaging equipment, data acquisition, processing, storage, and display now allow multidimensional imaging. Interactive computer programs can electronically display both static three-dimensional and higher-dimensional images that retain features such as motion, pressure, and temporal change. Multidimensional images can be reconstructed and manipulated using different holographic, stereolithographic, or interactive two-dimensional displays. We describe the unique potential of multidimensional reconstruction, virtual dissection, and replication of cardiovascular structures using ultrasound data. Ultrasound technology has the advantage of depicting both anatomy and physiology. The ability to perform virtual dissection and surgery in the living patient without disruption of anatomy or physiology provides the clinician with a powerful new tool for diagnosis, teaching, and therapeutics.