Reduced myocardial flow reserve in non-insulin-dependent diabetes mellitus

OBJECTIVES: We analyzed myocardial flow reserve (MFR) in patients with non-insulin-dependent (type II) diabetes mellitus (NIDDM) without symptoms and signs of ischemia. BACKGROUND: Diminished MFR in diabetes has been suggested. However, it remains controversial whether MFR is related to glycemic control, mode of therapy or gender in NIDDM. METHODS: Myocardial blood flow (MBF) was measured at baseline and during dipyridamole loading in 25 asymptomatic, normotensive, normocholesterolemic patients with NIDDM and 12 age-matched control subjects by means of positron emission tomography and nitrogen-13 ammonia, after which MFR was calculated. RESULTS: Baseline MBF in patients with NIDDM ([mean +/- SD] 74.0 +/- 24.0 ml/min per 100 g body weight) was comparable to that in control subjects (73.0 +/- 17.0 ml/min per 100 g). However, MBF during dipyridamole loading was significantly lower in patients with NIDDM (184 +/- 99.0 ml/min per 100 g, p < 0.01) than in control subjects (262 +/- 120 ml/min per 100 g), as was MFR (NIDDM: 2.77 +/- 0.85; control subjects: 3.8 +/- 1.0, p < 0.01). A significantly decreased MFR was seen in men (2.35 +/- 0.84) compared with women with NIDDM (3.18 +/- 0.79, p < 0.05); however, no significant differences were found in terms of age, hemoglobin a1c and baseline MBF. MFR was comparable between the diet (2.78 +/- 0.80) and medication therapy groups (2.76 +/- 0.77) and was inversely correlated with average hemoglobin A1c for 5 years (r = -0.55, p < 0.01) and fasting plasma glucose concentration (r = -0.57, p < 0.01) but not age or lipid fractions. CONCLUSIONS: Glycemic control and gender, rather than mode of therapy, is related to MFR in NIDDM.     

Reduced coronary flow reserve in familial hypercholesterolemia

Familial hypercholesterolemia (FH) presents the highest risk for coronary artery disease (CAD) among patients with hyperlipidemia. Therefore, early detection of coronary arterial atherosclerosis is important for the treatment of FH patients. The aim of this study was to detect early coronary arterial abnormalities that may relate to future atherosclerosis in asymptomatic FH patients by measuring coronary flow reserve (CFR) using PET and 13N-ammonia. METHODS: Twenty-five patients with FH (14 men, 11 women) without a history of myocardial ischemia and 14 control subjects (9 men, 5 women) were studied. Total serum cholesterol (mmole/liter) was 5.33 +/- 0.66 in control subjects and 7.90 +/- 0.77 in FH patients (p < 0.01 versus control subjects). RESULTS: Myocardial blood flow (MBF) at rest and during dipyridamole loading was measured using PET, and CFR was calculated. MBF (ml/min/100 g weight heart) at rest in the FH group (79.0 +/- 20.0) was comparable to that in control subjects (70.0 +/- 17.0). However, MBF during dipyridamole loading was significantly lower in FH patients (163.0 +/- 67.0) than in control subjects (286.0 +/- 120.0, p < 0.01). CFR in FH patients (2.09 +/- 0.62) was also significantly lower than that in control subjects (4.13 +/- 1.38, p < 0.01). CFR showed a gender-specific variance in FH patients (1.85 +/- 0.40 in men versus 2.55 +/- 0.74 in women p < 0.05) but not in control subjects. Significant inverse correlations between CFR and the total plasma cholesterol level as well as plasma LDL cholesterol were observed. CONCLUSION: The CFR was reduced in patients with FH. This abnormality was more prominent in men than in women patients. Noninvasive assessment of CFR by 13N-ammonia PET was useful to detect early abnormalities of the coronary arteries in asymptomatic patients with FH.     

Global alteration in perfusion response to increasing oxygen consumption in patients with single-vessel coronary artery disease

BACKGROUND: Recent evidence suggests that, in coronary artery disease (CAD), myocardial blood flow (MBF) regulation is abnormal in regions supplied by apparently normal coronary arteries. However, the relation between this alteration and MBF response to increasing metabolic demand has not been fully elucidated. METHODS AND RESULTS: MBF was assessed at baseline, during atrial pacing tachycardia, and after dipyridamole (0.56 mg/kg IV over 4 minutes) in 9 normal subjects and in 24 patients with ischemia on effort, no myocardial infarction, and isolated left anterior descending (n = 19) or left circumflex (n = 5) coronary artery stenosis (> or = 50% diameter narrowing). Perfusion of both poststenotic (S) and normally supplied (N) areas was measured off therapy by positron emission tomography and [13N]ammonia. Normal subjects and CAD patients showed similar rate-pressure products at baseline, during pacing, and after dipyridamole. In CAD patients, MBF was lower in S than in N territories at rest (0.68 +/- 0.14 versus 0.74 +/- 0.18 mL.min-1.g-1, respectively, P < .05), during pacing (0.92 +/- 0.29 versus 1.16 +/- 0.40 mL.min-1.g-1, respectively, P < .01), and after dipyridamole (1.18 +/- 0.34 versus 1.77 +/- 0.71 mL.min-1.g-1, respectively, P < .01). However, normal subjects showed significantly higher values of MBF both at rest (0.92 +/- 0.13 mL.min-1.g-1, P < .05 versus both S and N areas), during pacing tachycardia (1.95 +/- 0.64 mL.min-1.g-1, P < .01 versus both S and N areas), and after dipyridamole (3.59 +/- 0.71 mL.min-1.g-1, P < .01 versus both S and N areas). The percent change in flow was strictly correlated with the corresponding change in rate-pressure product in normal subjects (r = .85, P < .01) but not in either S (r = .04, P = NS) or N regions (r = .08, P = NS) of CAD patients. CONCLUSIONS: Besides epicardial stenosis, further factors may affect flow response to increasing metabolic demand and coronary reserve in patients with CAD.     

The graft flow and 201Tl-myocardial scintigram in patients with saphenous vein graft or left internal thoracic artery graft

To evaluate myocardial perfusion in patients with saphenous vein graft (SVG) or internal thoracic artery graft (ITA-G), we studied 38 patients (14: SVG, 10 males and 4 females, mean age 66 +/- 9 y-o; 24: ITA-G, 18 males and 6 females, mean age 64 +/- 7 y-o) by digital subtraction angiography (DSA) of ITA-G or SVG, and thallium-201 myocardial perfusion scintigraphy on exercise or dipyridamole stress. The grafting sites were left anterior descending artery (LAD) in all patients. Normal controls (n = 22) were defined by normal coronary angiogram and no evidence of myocardial ischemia. The graft flow and flow reserve on dipyridamole were measured by Rutishauser's formula. The basal blood flow of native normal ITA, SVG and ITA-G were respectively 72 +/- 24 ml/min, 51 +/- 23 ml/min, and 36 +/- 20 ml/min. The basal ITA-G flow was significantly lower than SVG-flow (p < 0.05). The flow reserves of SVG and ITA-G were respectively 2.32 +/- 0.65 and 1.78 +/- 0.59 (p < 0.02). The incidence of moderate hypoperfusion of thallium-201 SPECT was 14.3% in SVG and 12.5% in ITA-G on exercise stress, and 35% in SVG and 50% in ITA-G on dipyridamole stress. The incidence of reversible myocardial ischemia on dipyridamole stress was significant. The graft flow in patients with normal and abnormal thallium-201 SPECT were respectively 61 +/- 21 ml/min and 33 +/- 15 ml/min in SVG (p < 0.01), 46 +/- 19 ml/min and 27 +/- 16 ml/min in ITA-G (p < 0.02). The graft flow reserve were respectively 2.69 +/- 0.38 and 1.65 +/- 0.49 in SVG (p < 0.001), 2.25 +/- 0.40 and 1.31 +/- 0.28 in ITA-G (p < 0.001). We concluded that the basal blood flow and flow reserve of ITA-G were significantly lower than those of SVG. The myocardial ischemia was occasionally documented by the thallium-201 myocardial SPECT on dipyridamole stress in patients with patent ITA-G.     

Dipyridamole stress echocardiography and exercise testing for risk stratification after uncomplicated myocardial infarction

BACKGROUND: Risk stratification for subsequent cardiac events after an acute infarction can be obtained by exercise testing or dipyridamole stress echocardiography. It remains to be determined whether these modalities are equivalent and provide incremental information on top of clinical evaluation. The aim of our study was to compare the prognostic information obtained early after an acute uncomplicated myocardial infarction of high dose dipyridamole coupled with echocardiography (stress echo) or maximal symptom-limited exercise testing. METHODS AND RESULTS: Ninety patients underwent dipyridamole stress echo and exercise testing at a mean +/- SD of 9 +/- 4 days after admission for acute uncomplicated first myocardial infarction. All patients were prospectively followed for 22 +/- 16 months. There were 9 hard events (3 cardiac deaths and 6 acute myocardial infarctions) and 12 soft events due to post MI angina (6 angioplasty and 6 bypass surgery procedures). Univariate predictor of hard events was rest-stress wall motion score index variation (p = 0.009); univariate predictors of all events (hard + soft) were: positive exercise testing (p = 0.001), positive stress echo (p = 0.001), rest-stress wall motion score index variation (p = 0.002), extent of ischemia at echo (p = 0.008). Multivariate analysis by Cox selected a non-Q wave infarction and rest-stress wall motion score index variation as predictors of death or reinfarction (overall chi-square for the model 12.2, p = 0.0022). CONCLUSIONS: Stress echo is superior to ergometric variables for predicting events after uncomplicated myocardial infarction.     

Alterations of the architecture of subendocardial arterioles in patients with hypertrophic cardiomyopathy and impaired coronary vasodilator reserve: a possible cause for myocardial ischemia

OBJECTIVES: The study was designed to investigate the architecture of subendocardial arterioles of patients with hypertrophic cardiomyopathy (HCM) and angina pectoris with respect to coronary vasodilator reserve. BACKGROUND: There is growing evidence that the coronary microvasculature is abnormal in HCM. Arterioles, which mainly regulate intramyocardial blood flow, are especially suspect. METHODS: Thirteen patients with HCM (50.1+/-12.6 years old, mean value +/- SD) were studied after exclusion of any relevant coronary stenoses. Subendocardial arterioles (density [n/mm2], wall area [microm2], percent lumen area [%lumen], periarteriolar collagen area [microm2]), myocyte diameter (microm) and interstitial collagen fraction (Vv%) were evaluated by means of stereologic morphometry of transvenous biopsy samples. Coronary blood flow was measured quantitatively with the inert chromatographic argon method at basal conditions and after dipyridamole (0.5 mg/kg body weight over 4 min intravenously), and coronary vasodilator reserve was calculated as the ratio of coronary resistance at basal conditions and after pharmacologic vasodilation. Data from five normotensive subjects (45.4+/-11 years old, p = NS) served as control data. RESULTS: Arteriolar density was diminished by 38% (p = 0.004) and %lumen by 13% (p = 0.009) in patients with HCM compared with control subjects. Coronary reserve was impaired in patients with HCM (2.28+/-0.6 vs. 5.34+/-1.49, p = 0.003) because of higher coronary resistance after vasodilation (0.48+/-0.14 vs. 0.22+/-0.06 mm Hg x min x 100 g/ml, p = 0.004). Coronary vasodilator reserve correlated with arteriolar density (r = +0.47, p = 0.045) and with %lumen (r = 0.65, p = 0.003). CONCLUSIONS: In HCM, the architecture of preterminal subendocardial arterioles is altered by a reduced total cross-sectional lumen area, corresponding to an impaired coronary vasodilator capacity that may predispose to myocardial ischemia.     

Significance of myocardial ischemic electrocardiographic changes during dipyridamole stress echocardiography

The aim of this study was to assess the diagnostic and prognostic value of the presence and characteristics of ischemic electrocardiographic (ECG) changes during dipyridamole stress echocardiography. The ECG response in 178 patients with echocardiographic evidence of myocardial ischemia during dipyridamole stress testing was analyzed. ECG changes occurred in 105 patients (59%). Patients with ECG changes had a higher incidence of echocardiographic signs of ischemia at a low dose than patients with an unchanged electrocardiogram (50% vs 23%; p = 0.0002). Three-vessel and/or left main coronary artery disease (CAD) was found in 41% of patients with and in 21% of patients without ECG changes (p = 0.029). During follow-up (33 +/- 19 months), 30 cardiac events occurred: 10 deaths, 6 infarctions, and 14 unstable anginas. Coronary revascularization was performed in 48 patients with and in 17 patients without ECG changes (p = 0.0022). The univariate predictors of cardiac events were: presence of ischemia in > or =4 ECG leads (p = 0.0004), echocardiographic evidence of ischemia at a low dose (p = 0.0062), ST-segment shift on precordial leads (p = 0.0094), family history of CAD (p = 0.0115), coexistence of > or =3 cardiovascular risk factors (p = 0.0156), ST-segment depression (p = 0.0172), and ECG changes during testing (p = 0.0335). At Cox analysis, occurrence of ischemia at a low dose (odds ratio 3.0; 95% confidence interval 1.3 to 6.8) and the presence of ischemia in > or =4 ECG leads (odds ratio 3.5; 95% confidence interval 1.3 to 9.3) had an independent prognostic importance. In conclusion, the presence and characteristics of ischemic ECG changes are associated with more extensive CAD and worse prognostic outlook than are echocardiographic changes alone during dipyridamole stress echocardiography.     

Gender differences in myocardial blood flow dynamics: lipid profile and hemodynamic effects

OBJECTIVES: The purpose of the study was to compare myocardial blood flow (MBF) in hyperlipidemic postmenopausal women and age-matched hyperlipidemic men, and to analyze the relationship between cholesterol subfractions and myocardial blood flow in men and women. BACKGROUND: Women are protected from coronary artery disease (CAD) events until well after menopause, in part due to gender-specific differences in lipid profiles. METHODS: To examine the effect of these influences on coronary microcirculation, MBF was quantitated with N-13 ammonia/PET (positron emission tomography) at rest and during adenosine hyperemia in 15 women and 15 men, all nondiabetic, who were matched for age and total cholesterol levels (53+/-4 vs. 50+/-8 years, p = NS, 6.44+/-1.1 vs. 6.31+/-0.85 mmol/liter, or 249+/-41 vs. 244+/-33 mg/dl, p = NS). RESULTS: Women had significantly higher high density lipoprotein (HDL) and lower triglyceride (Tg) levels than did men, and they showed significantly higher resting MBF and stress MBF levels. Significant correlations were found between resting and hyperemic MBF and HDL and Tg levels (r = 0.44, p < 0.02 for stress MBF vs. HDL; r = 0.48, p < 0.007 for stress MBF vs. Tg). Gender was the strongest predictor of hyperemic MBF in multivariate analysis. Women responded to adenosine hyperemia with a significantly higher heart rate than did men, and hemodynamic factors correlated significantly with blood flow both at rest and during stress. CONCLUSIONS: These data suggest that the favorable lipid profile seen in women may be associated with preserved maximal blood flow in the myocardium.     

Flow versus uptake comparisons of thallium-201 with technetium-99m perfusion tracers in a canine model of myocardial ischemia

We investigated the myocardial flow kinetics of six putative radioperfusion agents (99mTc-Q3, 99mTc-Q4, 99mTc-Q12, 99mTc-sestamibi, 99mTc-tetrofosmin and 99mTcN-NOET) and 201Tl in a canine model of myocardial ischemia with pharmacologic coronary artery vasodilation. METHODS: In 31 open-chest dogs with acute coronary occlusion, dipyridamole (approximately 0.56 mg/kg) was infused intravenously, followed by a perfusion tracer injection and radioactive microspheres for myocardial blood flow (MBF) measurement. The paired data were normalized using three techniques; average, normal or maximum myocardial tracer activity and MBF. RESULTS: The upper limit of MBF obtained for the group of tracers ranged from 4.2 ml/min/g to 8.2 ml/min/g. There was a statistically significant (p < 0.0001) linear correlation (r = 0.87-0.98) between the normalized myocardial activity and the normalized MBF values of each of the tracers. The slope of the curve normalized by average for 201Tl (0.83) was greater than those for the 99mTc tracers, and the intercept (0.07) was lower than those for the 99mTc tracers. Slopes and intercepts for the 99mTc agents were as follows: 99mTc-Q3, 0.81 and 0.18; 99mTc-Q4, 0.61 and 0.41; 99mTc-Q12, 0.63 and 0.39; 99mTc-sestamibi, 0.62 and 0.34; 99mTc-tetrofosmin, 0.68 and 0.32; and 99mTcN-NOET, 0.71 and 0.29, respectively. CONCLUSION: In an anesthetized open-chest canine model of regional myocardial ischemia with dipyridamole induced hyperemia, 201Tl shows a more ideal relationship between tracer uptake and MBF than do the 99mTc-based agents. Of the various 99mTc-based imaging agents studied, the myocardial flow kinetics of 99mTc-Q3 appear to be closest to ideal. This relationship is maintained regardless of the normalization technique used. This may, in theory, imply a higher sensitivity in discerning ischemic from normal myocardium and a role in diagnostic nuclear imaging for 99mTc-Q3.     

Underestimation of extent and severity of coronary artery disease by dipyridamole stress thallium-201 single-photon emission computed tomographic myocardial perfusion imaging in patients taking antianginal drugs

OBJECTIVES: This study evaluated the diagnostic value of dipyridamole plus low level treadmill exercise (dipyridamole stress) thallium-201 single-photon emission computed tomography (SPECT) in patients taking antianginal drugs. BACKGROUND: Dipyridamole stress is the major substitute for maximal exercise in patients referred for myocardial perfusion imaging. Although antianginal drugs are commonly suspended before exercise, dipyridamole stress is usually performed without discontinuing these drugs. METHODS: Twenty-six patients underwent two dipyridamole perfusion studies: the first without (SPECT-1) and the second with (SPECT-2) antianginal treatment. Twenty-one patients (81%) received calcium antagonists, 19 (73%) received nitrates, and 8 (31%) received beta-blockers. Eighteen of the patients underwent coronary angiography. Data are presented as the mean value +/- SD. RESULTS: Visual scoring yielded significantly larger and more severe reversible perfusion defects for SPECT-1 than for SPECT-2. Quantitative analysis showed larger perfusion defects on stress images of SPECT-1 in the left anterior descending coronary artery (LAD) (25 +/- 21% vs. 17 +/- 15%, p = 0.003), left circumflex coronary artery (LCx) (56 +/- 35% vs. 48 +/- 36%, p = 0.03) and right coronary artery (RCA) (36 +/- 27% vs. 25 +/- 24%, p = 0.008) territories. Individual vessel sensitivities in the LAD, LCx and RCA territories were 93%, 79% and 100% for SPECT-1 and 64%, 50% and 70% for SPECT-2, respectively. These differences were highly significant for the LAD (p = 0.004) and LCx (p = 0.00004) territories. The overall individual vessel sensitivity of SPECT-1 was significantly higher than that of SPECT-2 (92% vs. 62%, p = 0.000003). Specificity was not significantly different in SPECT-1 compared with SPECT-2 (80% and 93%, p = 0.33). CONCLUSIONS: Continued use of antianginal drugs before dipyridamole plus low level treadmill exercise thallium-201 SPECT may reduce the extent and severity of myocardial perfusion defects, resulting in underestimation of coronary artery disease.     

Impact of resting and ischemic blood flow on infarct probability in ischemic preconditioning--a new approach to infarct size-blood flow data by logistic regression

The linear regression analysis of infarct size (IS) v ischemic myocardial blood flow (MBF) does not account for the heterogeneity of MBF and infarcted tissue; moreover, it cannot assess a blood flow threshold for infarction (MBFT) accurately, as with ischemic preconditioning (IP) the close relationship between ischemic MBF and IS otherwise observed is lost. Finally, the impact of resting blood flow on myocardial infarction cannot be considered in such analysis. Therefore, in a retrospective data analysis of 32 enflurane-anaesthetized swine undergoing 90 min severe ischemia and 120 min reperfusion without (CON, n = 12) or with IP induced by either 3 (IP3, n = 8) or 10 min ischemia (IP10, n = 12) and 15 min reperfusion, a MBFT was assessed by logistic regression (LR) in individual tissue pieces. MBFT was arbitrarily defined as that ischemic MBF (microspheres) at which infarct probability was 0.2, derived from the ratio of infarcted (n = 141, TTC) to all tissue samples (n = 684). The duration of the preconditioning ischemia and MBF both at rest and during the sustained ischemia were significant predictors of infarct probability. Ischemic MBFT at an infarct probability of 0.2, was 0.089 +/- 0.023 ml/min/g in CON. MBFT was decreased to 0.051 +/- 0.03 ml/min/g with IP3 (P < 0.05 v CON) and further to 0.004 +/- 0.037 ml/min/g with IP10 (P < 0.05 v CON, IP3). Corresponding to the leftward shift of MBFT, the relationships between infarct probability and MBF were shifted in parallel by IP with no change in their slopes.     

Effects of ergotamine on myocardial blood flow in migraineurs without evidence of atherosclerotic coronary artery disease

The effects of intravenous ergotamine (0.25 mg) on basal and hyperemic (dipyridamole) myocardial blood flow (MBF), measured with positron emission tomography and H2(15)O, were assessed in 15 migraineurs in a double-blind, randomized, placebo controlled, crossover study. Ergotamine produced a 27% reduction in hyperemic MBF (2.62 +/- 0.11 vs 3.72 +/- 1.05 ml x min(-1) x g(-1); p <0.05), a 31% reduction in the coronary vasodilator reserve (1.81 +/- 0.50 vs 2.71 +/- 1.15; p <0.01), and a 55% increase in minimal coronary resistance (42.2 +/- 15 vs 26.7 +/- 8 mm Hg x min x ml(-1) x g(-1); p <0.001), suggesting vasoconstriction of the coronary microcirculation.     

Effects of ischemia, preconditioning, and adenosine deaminase inhibition on interstitial adenosine levels and infarct size

In order to examine the relationship between local adenosine concentrations before, during, and after ischemia and the extent of ischemic myocardial damage, measurements of interstitial fluid (ISF) nucleosides were made using microdialysis probes implanted in the ischemic region of isoflurane anesthetized Micropigs undergoing 60' coronary artery occlusion (CAO) and 3 h of reperfusion (REP). Nucleoside concentrations in the dialysate collected from the microdialysis probes were used as an index of ISF levels. Dialysate nucleoside concentrations (ADO, inosine and hypoxanthine), myocardial infarct size, and myocardial blood flow (MBF) were determined in control animals (n = 6), animals preconditioned with a single 10' cycle of CAO and REP (PC, n = 6), and those treated with the adenosine deaminase inhibitor pentostatin (n = 6, 0.2 mg/Kg i.v. 30' prior to CAO). The brief PC occlusion resulted in a transient but significant increase in dialysate ADO (6.7 +/- 1.8 microM vs. 0.67 +/- 0.1 microM at baseline). Pentostatin administration had no significant effect on either dialysate nucleosides or MBF at baseline. During the 60' CAO, dialysate ADO increased in control animals. In PC animals, however, dialysate ADO during CAO was lower than control. Pretreatment with pentostatin resulted in a six-fold augmentation in dialysate ADO during the 60 min CAO when compared to the control values (110.62 +/- 30.2 microM vs. 16.31 +/- 2.1 microM at 60 min of ischemia). Pentostatin also resulted in a significant reduction in the accumulation of inosine and hypoxanthine, indicating inhibition of adenosine deaminase activity. There were no significant differences in MBF between groups at any time point. Following 3 h REP, infarct size was 35.4 +/- 5.5%, 8.1 +/- 1.5% and 8.3 +/- 1.8% of the region at risk in control, PC, and pentostatin groups, respectively. These data suggest that marked increase in ISF ADO during CAO, may be as effective in reducing INF as a modest increase in ISF ADO prior to prolonged CAO.     

Prevalence of hyperapobetalipoproteinemia and other lipoprotein phenotypes in men (aged < or = 50 years) and women (< or = 60 years) with coronary artery disease

The prevalence and clinical characteristics of hyperapobetalipoproteinemia (hyperapoB) and other phenotypes of dyslipoproteinemia were examined in 99 men (aged < or = 50 years) and 104 women (< or = 60 years) undergoing elective diagnostic coronary arteriography. HyperapoB was the most common phenotype (34%) associated with premature coronary artery disease (CAD). Only 20.2% of patients with CAD had a normal lipoprotein phenotype. The significant odds ratios for CAD were as follows: hypertriglyceridemic hyperapoB 17.45 (p < 0.0001), type IV 6.54 (p = 0.0001), type IIa 4.73 (p = 0.008), normotriglyceridemic hyperapoB 2.54 (p = 0.03) and type IIb 8.73 (p = 0.05). The strong association of hypertriglyceridemic hyperapoB with CAD reflected the multiplicative effect of increased low-density lipoprotein apolipoprotein B and endogenous hypertriglyceridemia, and was independent of the effects of age, sex, diabetes mellitus, systemic hypertension, body mass index and cigarette smoking. The ratio of apolipoprotein B to A-1 was better than those of low-density to high-density lipoprotein cholesterol and total to high-density lipoprotein cholesterol at discriminating dyslipidemic phenotypes from normal. Obesity was increased approximately 1.5 to two-fold in the hypertriglyceridemic phenotypes, diabetes was more prevalent in hypertriglyceridemic hyperapoB (6.8-fold; p < 0.001) and type IV (4.4-fold; p = 0.02), and hypertension was increased 1.5- to twofold in most dyslipidemic groups. The data indicate that hyperapoB and endogenous hypertriglyceridemia both contribute to the risk of premature CAD.     

Chemical, physical, and sensory characteristics of mozzarella cheese fortified using protein-chelated iron or ferric chloride

OBJECTIVE: Short-term myocardial hibernation is characterized by an adaptation of contractile function to the reduced blood flow, the recovery of creatine phosphate content and lactate balance back towards normal, whereas ATP content remains reduced at a constant level. We examined the hypothesis that, despite the absence of ATP recovery, the short-term hibernating myocardium regains an energetic balance. METHODS: An enzymatic method was modified for the measurement of inorganic phosphate (Pi) in transmural myocardial drill biopsies (about 5 mg). In 12 anaesthetized swine, moderate ischemia was induced by reduction of coronary inflow into the cannulated left anterior descending coronary artery to decrease regional myocardial function (sonomicrometry) by 50%. RESULTS: The development of short-term hibernation was verified by the recovery of creatine phosphate content, the persistence of inotropic reserve in response to dobutamine and the absence of necrosis (triphenyl tetrazolium chloride). At 5-min ischemia, Pi was increased from 3.6 +/- 0.3 (SD) to 8.1 +/- 1.1 mumol/gwet wt (p < 0.05). The free energy of ATP hydrolysis (delta GATP) was decreased from -57.8 +/- 0.8 to -52.2 +/- 1.4 kJ/mol (p < 0.05). The relationships between function and Pi (r = -0.81) and delta GATP (r = -0.83), respectively, during control and at 5-min ischemia became invalid at 90-min ischemia, as myocardial blood flow and function remained reduced at a constant level, but Pi decreased back to 4.9 +/- 0.9 mumol/g (p < 0.05 vs. control and 5-min ischemia), and delta GATP fully recovered back to -57.2 +/- 1.3 kJ/mol (p < 0.05 vs. 5-min ischemia). CONCLUSIONS: In short-term hibernating myocardium, myocardial inorganic phosphate content recovers partially and the free energy change of ATP hydrolysis returns to control values. Contractile function remains reduced by mechanisms other than an energetic deficit.     

Preservation of regional myocardial function and myocardial oxygen tension during acute ischemia in pigs: comparison of selective synchronized suction and retroinfusion of coronary veins to synchronized coronary venous retroperfusion

OBJECTIVES: The efficacy of selective synchronized suction and retroinfusion of coronary veins was compared with synchronized coronary venous retroperfusion in preventing ischemic reduction of regional myocardial function and myocardial oxygen tension. BACKGROUND: Because incomplete protection by synchronized coronary venous retroperfusion during ischemia might result from nonselective retroinfusion and only passive drainage of the veins, a suction device was added to a retroinfusion system. METHODS: Regional myocardial function (ultrasonic crystals) and myocardial oxygen tension (polarographic electrodes) were studied in 30 pigs during 10-min occlusion of the left anterior descending coronary artery (ischemia), followed by reperfusion. During ischemia, group A (n = 10) was supported by selective synchronized suction and retroinfusion; group B (n = 10) was supported by synchronized coronary venous retroperfusion, and group C (n = 10) was not supported by retroinfusion. RESULTS: In group A, subendocardial segment shortening decreased from 21 +/- 4% (mean +/- SD) before ischemia to 11 +/- 5% during ischemia. In contrast, systolic dyskinesia was observed in group B (-2 +/- 4%, p < 0.001) and group C (-2 +/- 5%, p < 0.001). During ischemia, the decrease in intramyocardial oxygen tension was less pronounced in group A (41 +/- 15 vs. 27 +/- 12 mm Hg) than in group B (40 +/- 10 vs. 19 +/- 10 mm Hg, p = 0.1) or group C (33 +/- 11 vs. 12 +/- 8 mm Hg, p = 0.002). During ischemia, myocardial surface oxygen tension was preserved > 0 mm Hg only in group A. CONCLUSIONS: Preservation of regional myocardial function and myocardial oxygen tension was substantially higher by selective synchronized suction and retroinfusion of coronary veins than by synchronized coronary venous retroperfusion in pigs.     

The potential benefit of a home fire safety intervention during emergency medical services calls

The clinical significance of silent myocardial ischemia (SMI) in the elderly was assessed in 91 patients with Q wave infarction who showed ischemic ST depression during treadmill stress testing, as well as reversible defect (RD) during dipyridamole thallium imaging. They were divided into two groups (47 patients with silent ST depression and 44 patients with painful ST depression) and compared for scintigraphic and coronary arteriographic features, and prognosis. There was no significant difference in age, gender and site of infarction between the two groups. The prevalence of single and double vessel coronary stenosis was higher in patients with SMI (66%) than in those with painful ischemia (p < 0.05). The results of treadmill stress testing showed a longer exercise duration (4.7 +/- 1.7 vs. 4.1 +/- 1.8 min) and higher maximal heart rate (138 +/- 15/vs. 126 +/- 20/min) in patients with SMI than in those with painful ischemia (p < 0.01). Dipyridamole thallium imaging revealed a larger infact (18.8 +/- 9.1 vs. 14.6 +/- 10.2 segments) in patients with SMI than in those with painful ischemia (p < 0.05). The prevalence of RD in the area of infarction was also higher in patients with SMI (74%) than in those with painful ischemia (45%) (p < 0.05). Although a higher proportion of the patients with painful ischemia (42%) underwent CABG or PTCA as their initial therapy, compared with those with SMI (25%) (ns), there was no difference in the cardiac event rate between the two groups who were initially treated medically. Dipyridamole thallium imaging is useful in the assessment of SMI in elderly patients with Q wave myocardial infarction. Those with SMI may have a larger infarct and a higher prevalence of ischemia localized within the infarction than those with painful ischemia.     

Academic underachievement in ADHD subtypes

Excessive production of cholesterol has been associated with type IV hyperlipidemia, but the influence of the confounding variable of obesity has been difficult to ascertain. Moreover, cholesterol metabolism has not been systematically evaluated in patients with familial hypertriglyceridemia (FHT), one of the two major subsets of type IV patients. We used isotope dilution to measure cholesterol production, pools, and kinetic constants in 8 hypertriglyceridemic subjects, 6 of whom could be confidently classified as FHT. These were compared with measurements in 9 control subjects matched for sex, age, serum cholesterol, and body mass index (BMI). By t test, hypertriglyceridemic subjects did not differ from controls with respect to cholesterol production, size of readily or slowly miscible pools, or kinetic transfer coefficients. Results were the same whether controls were compared with all hypertriglyceridemic patients or only the 6 with definite FHT. By analysis of covariance (ANCOVA), serum triglyceride level was not a significant determinant of any parameter of cholesterol metabolism. However, BMI was a highly significant determinant of cholesterol production (p = 0.0001) and size of both readily and slowly miscible pools (p = 0.001 to 0.008). These data suggest that FHT per se is not associated with abnormalities of cholesterol metabolism but that an apparent association could result from the confounding variable of obesity.     

Myocardial perfusion reserve studied by single-photon emission-computed tomography with thallium-201 and a drug stress test with adenosine triphosphate in patients with cardiovascular risk factors

INTRODUCTION AND OBJECTIVE: Recent studies have suggested that the evaluation of coronary reserve is a sensitive method in the early detection of vascular alterations before plaques exist, and certainly before clinical detection of atherosclerotic lesions. Single-photon emission-computed tomography (SPECT) with thallium-201 (201Tl) provides a noninvasive tool for evaluating myocardial perfusion reserve. The objective of this study was to measure the myocardial perfusion reserve in two groups of subjects, some with and some without cardiovascular risk factors and in a group of patients with coronary artery disease. METHODS: Seventy-four subjects, divided into three groups, were recruited to assess regional and global myocardial perfusion reserve. The control group consisted of 11 asymptomatic individuals without cardiovascular risk factors. The second group was composed of 49 patients with one or more risk factors. Finally, the third group included 14 patients with coronary artery disease. 201Tl-SPECT at rest and after pharmacological stress with a 7 minute adenosine triphosphate (ATP) infusion (140 micrograms/kg/min) was performed in all patients. ATP minus rest value subtraction was applied in order to obtain the stress data. Relative myocardial perfusion reserve indices were calculated as the ratio between stress and rest values. RESULTS: Global and regional myocardial perfusion reserves of the vascular territories were significantly lower in patients with cardiovascular risk factors than in control subjects (Global: 1.48 +/- 0.19 vs 1.81 +/- 0.08, LAD: 1.52 +/- 0.21 vs 1.85 +/- 0.09, CX: 1.45 +/- 0.2 vs 1.79 +/- 0.86, RCA: 1.47 +/- 0.2 vs 1.79 +/- 0.86) and higher than in patients with coronary artery disease (Global: 1.48 +/- 0.19 vs 1.31 +/- 0.14, LAD: 1.52 +/- 0.21 vs 1.35 +/- 0.15, CX: 1.45 +/- 0.2 vs 1.2 +/- 0.24). Univariate linear regression analysis in a group of 40 patients with high risk lipid profiles revealed a significant negative correlation between myocardial perfusion reserve and total cholesterol (r = -0.35; p = 0.01), LDL-cholesterol (r = -0.38; p = 0.036) and LDL/HDL ratio (r = -0.39; p = 0.029). CONCLUSION: Determination of myocardial perfusion reserve with 201Tl-SPECT allows the detection of abnormal vasodilatory response to intravenous ATP in patients with cardiovascular risk factors. These patients have higher reserves than patients with coronary disease, which might suggest an early phase of atherosclerosis.     

Abnormality of myocardial oxidative metabolism in noninsulin-dependent diabetes mellitus

The purpose of this study was to evaluate oxidative metabolism and its response by dobutamine in patients with noninsulin-dependent diabetes mellitus (NIDDM) using 11C-acetate PET. METHODS: We studied 16 patients with NIDDM (9 men, 7 women; mean age 53.7 +/- 12.8 yr) and 6 healthy male control subjects (mean age 41.8 +/- 17.2 yr). None of them had an abnormality on stress-perfusion SPECT. The 11C-acetate clearances (Kmono) were compared regionally for five myocardial segments in all subjects at rest and during low-dose dobutamine stress in 13 patients (8 patients with NIDDM, age 51.9 +/- 13.6 yr; 5 healthy male control subjects, age 45.6 +/- 16.3 yr). Correlation between regional Kmono and rate-pressure product (RPP) was also studied. RESULTS: At rest, the clearance of 11C-acetate was slightly heterogeneous for both patients with NIDDM and healthy control subjects, with smaller values in the apex and inferior wall in both groups. The difference became significant during dobutamine stress in the patients. The RPP-to-Kmono (average for five segments) ratio at rest was slightly smaller in the patients (1042.7 +/- 559.1 x 0.01) than in the healthy control subjects (1391.4 +/- 209.6 x 0.01, not significant), and those during dobutamine stress were almost the same in the two groups (1457.3 +/- 737.4 x 0.01 and 1486.0 +/- 211.8 x 0.01, respectively). A significant correlation was seen between regional Kmono and RPP in every segment in the healthy control subjects (average; r = 0.89; p < 0.01), whereas more scattered correlation with greater regional variation was observed in the patients (average; r = 0.31; p value was not significant). CONCLUSION: Patients with NIDDM showed slight regional heterogeneity in myocardial oxidative metabolism. They also had more scattered correlation between myocardial oxidative metabolism and cardiac work (RPP) than healthy control subjects, with the smallest correlation coefficient observed in the inferior wall. These findings may help the understanding of dynamics in myocardial oxidative metabolism of NIDDM hearts.