Basal Myocardial Blood Flow Research Articles

Reduced Myocardial Perfusion Reserve in Type 2 Diabetes Is Caused by Increased Perfusion at Rest and Decreased Maximal Perfusion During Stress.

To examine differences in myocardial blood flow (MBF) at rest and during stress between patients with type 2 diabetes and control subjects, and to identify potential predictors of changes in MBF at rest and during stress. A cross-sectional study was conducted of 193 patients with type 2 diabetes and 20 age- and sex-matched control subjects. Cardiovascular magnetic resonance was used to evaluate left ventricular structure and function and MBF at rest and during adenosine-induced stress. MBF was derived as the mean of the flow within all segments of a midventricular slice. Patients with type 2 diabetes had higher global MBF at rest (0.81 ± 0.19 mL/min/g) and lower global MBF during stress (2.4 ± 0.9 mL/min/g) than control subjects (0.61 ± 0.11 at rest, 3.2 ± 0.8 mL/min/g under stress; both P < 0.01). Patients with macroalbuminuria had lower MBF during stress (1.6 ± 0.5 mL/min/g) than did patients with microalbuminuria (2.1 ± 0.7 mL/min/g; P = 0.04), who in turn had lower MBF during stress than did normoalbuminuric patients (2.7 ± 0.9 mL/min/g; P < 0.01). Patients with severe retinopathy had lower MBF during stress (1.8 ± 0.6 mL/min/g) than patients with simplex retinopathy (2.3 ± 0.7 mL/min/g; P < 0.05) and those who did not have retinopathy (2.6 ± 1.0 mL/min/g; P < 0.05). Albuminuria and retinopathy were associated with reduced MBF during stress in a multiple regression analysis. Stress-related MBF inversely correlated with myocardial extracellular volume (P < 0.001; R 2 = 0.37), a measure of diffuse myocardial fibrosis. A trend toward lower basal MBF was observed in patients treated with sodium-glucose cotransporter 2 inhibitors (P = 0.07). Patients with type 2 diabetes have higher global MBF at rest and lower maximal MBF during vasodilator-induced stress than control subjects. Reduced MBF during stress is associated with diabetes complications (albuminuria and retinopathy) and is inversely correlated with diffuse myocardial fibrosis.

P4469Reduced myocardial perfusion reserve in type 2 diabetes is caused by increased rest perfusion as well as decreased maximal perfusion during stress

Abstract Background Reduced myocardial perfusion reserve is a well-known complication in patients with type 2 diabetes mellitus (T2DM). Furthermore, reduced myocardial perfusion reserve has been linked to the development of diastolic dysfunction, a key characteristic in diabetic cardiomyopathy. However, it is not fully explored whether a decrease in perfusion during stress or an increase in perfusion during rest is responsible for this reduction in myocardial perfusion reserve, nor is it clear what causes these changes. Purpose The purpose of this study was to examine differences in myocardial perfusion in rest and during stress in patients with T2DM compared to healthy control subjects, and to identify potential predictors for changes in perfusion during rest and stress among patients with T2DM. Methods 200 patients with T2DM and 25 healthy volunteers matched for age and sex underwent a comprehensive cardiac MRI protocol including gadolinium first-pass perfusion during rest and stress (adenosine infusion 140 mg/min–1/kg–1). Perfusion was measured on a per-segment basis based on the AHA model and averaged to calculate global perfusion index both during rest and stress. Any areas with infarctions and/or significant perfusion defects were excluded from the analysis. Backwards stepwise multiple linear regression was performed to identify predictors for perfusion changes during rest and stress in patients with T2DM. Variables with P&lt;0.1 in a univariate analysis were included into the models. Results Patients with T2DM had significantly higher rest perfusion index (0.135±0.024 vs. 0.120±0.016; P=0.001) and significantly lower stress perfusion index (0.174±0.041 vs. 0.225±0.027; P&lt;0.001) compared to healthy volunteers. In a multiple linear regression model among patients with T2DM female sex (P&lt;0.001) was associated with increased rest perfusion. In a similar analysis for stress perfusion, diabetes duration (P=0.01), albuminuria (P&lt;0.001) and the presence of ischaemic heart disease (P&lt;0.001) were associated with reduced myocardial stress perfusion index in patients with T2DM. Conclusion In patients with T2DM reductions in myocardial perfusion reserve is caused by a combination of increased basal myocardial blood flow and a decrease in maximal blood flow during stress. Decreased stress perfusion is associated with coronary vascular disease and the diabetic complication albuminuria related to renal microvascular disease. Stress perfusion also decreased with increasing duration of T2DM. This suggest that the coronary microcirculation is gradually damaged in patients with T2DM and that the mechanism responsible is similar to that causing renal microvascular damage. Acknowledgement/Funding Local science committee of Region Zealand, Regional science committee of Region Zealand, The Danish Heart Association

V˙O2peak, Myocardial Hypertrophy, and Myocardial Blood Flow in Endurance-Trained Men

Endurance training induces cardiovascular and metabolic adaptations, leading to enhanced endurance capacity and exercise performance. Previous human studies have shown contradictory results in functional myocardial vascular adaptations to exercise training, and we hypothesized that this may be related to different degrees of hypertrophy in the trained heart. We studied the interrelationships between peak aerobic power (V˙O2peak), myocardial blood flow (MBF) at rest and during adenosine-induced vasodilation, and parameters of myocardial hypertrophy in endurance-trained (ET, n = 31) and untrained (n = 17) subjects. MBF and myocardial hypertrophy were studied using positron emission tomography and echocardiography, respectively. Both V˙O2peak (P < 0.001) and left ventricular (LV) mass index (P < 0.001) were higher in the ET group. Basal MBF was similar between the groups. MBF during adenosine was significantly lower in the ET group (2.88 ± 1.01 vs 3.64 ± 1.11 mL·g·min, P < 0.05) but not when the difference in LV mass was taken into account. V˙O2peak correlated negatively with adenosine-stimulated MBF, but when LV mass was taken into account as a partial correlate, this correlation disappeared. The present results show that increased LV mass in ET subjects explains the reduced hyperemic myocardial perfusion in this subject population and suggests that excessive LV hypertrophy has negative effect on cardiac blood flow capacity.

Coronary microvascular dysfunction in primary cardiomyopathies

Myocardial ischaemia is usually caused by abnormalities of the epicardial coronary arteries. In the past 30 years, however, several studies have shown that abnormalities in the coronary microcirculation may also...

Why Quantify Myocardial Perfusion?

Myocardial blood flow (MBF) and coronary flow reserve (CFR), the ratio of MBF during hyperemia to basal MBF, are integrated measures of flow through both the large epicardial coronary arteries and the microcirculation. To date, positron emission tomography (PET) offers the most robust and best investigated method for quantifying MBF in vivo. The potential of MBF quantification to improve detection of patients with high-risk coronary artery disease (CAD) or to identify patients with variable degrees of microvascular or endothelial dysfunction are promising new clinical avenues which await further evaluation in larger prospective trials. The current experience with MBF quantification also demonstrates potential benefits in other groups of patients. The present article summarizes the published literature on MBF quantification in CAD and other cardiac conditions and outlines in which fields MBF quantification could offer important value to improve the treatment and prognosis of patients. Novel PET perfusion compounds that are not bound to an onsite cyclotron will improve availability of MBF quantification, promote its use in the clinical setting, and facilitate further studies to establish its clinical value.

Measurement of heritability of myocardial blood flow by positron emission tomography: the Twins Heart Study

ObjectiveTo estimate the heritability of myocardial blood flow (MBF) and coronary flow reserve (CFR) measured with positron emission tomography (PET).DesignCross-sectional twin study.SettingGeneral clinical research centre of a university hospital at...

Coronary Diameter and Vasodilator Function in Children Following Arterial Switch Operation for Complete Transposition of the Great Arteries

Coronary reimplantation during arterial switch operation (ASO) may affect coronary artery growth and function during childhood. The purpose of this study was to assess coronary artery diameter and regional myocardial blood flow (MBF) and myocardial flow reserve (MFR) in children after neonatal ASO. We measured proximal diameters of left anterior descending (LAD), left circumflex, and posterior descending coronary arteries on coronary angiogram in 12 children (median age 11 years, range 7.6 to 15.1) with a history of neonatal ASO. These children then underwent cardiac positron emission tomographic imaging using nitrogen-13 ammonia to assess MBF at baseline and during intravenous adenosine hyperemia in regions supplied by these 3 coronary arteries. Coronary artery z-scores were within normal range (-2.0 to 2.0) for 32 of 36 coronary arteries. MFR (ratio of hyperemic to basal MBF) was normal (>2.5) in all myocardial regions in 10 of 12 patients. The remaining 2 patients, 1 with a dual LAD and 1 with LAD origin from the right coronary artery, had generalized impairment of hyperemic MBF (<2.0 ml/g/min) and low MFR (<2.5). Coronary artery z-scores and MFR in corresponding myocardial territories were not correlated (r = 0.15, p = 0.36). In conclusion, coronary growth and function appear to be normal in most children after neonatal ASO. Children with anatomic LAD abnormalities may be at increased risk of impaired MFR.

Positive family history of coronary artery disease is associated with reduced myocardial vasoreactivity in healthy men

Objective Positive family history as a risk factor for coronary artery disease seems to be most important in subjects who otherwise are at low risk. We examined the association between family history of coronary artery disease and myocardial vasoreactivity in healthy men. Methods 35 non-smoking healthy men (age 35 ± 7 years) were studied: 16 had positive family history of coronary artery disease and 19 had negative family history. The myocardial blood flow measurements were performed basally and during adenosine infusion (140 μg/kg/min) with and without simultaneous physiological hyperinsulinemia (insulin infusion at a rate of 1 mU/kg/min) using positron emission tomography and O-15-water. Results Basal myocardial blood flow was similar between the subjects with positive and negative family history of coronary artery disease (0.79 ± 0.19 and 0.79 ± 0.21 mL g − 1 min − 1 , NS). Adenosine stimulated flow was significantly reduced in subjects with positive family history (3.0 ± 0.5 vs 4.0 ± 1.2 mL g − 1 min − 1 , respectively, p = 0.003). During physiological hyperinsulinemia adenosine stimulated flow was further enhanced in both groups but significantly blunted in subjects with positive family history (3.7 ± 0.9 vs 5.2 ± 1.5 mL g − 1 min − 1 , respectively, p = 0.001). These differences remained significant after simultaneous controlling for age, BMI, HbA1c, LDL-cholesterol, HDL-cholesterol and blood pressure ( p = 0.002). Conclusions Healthy non-smoking men with positive family history of coronary artery disease are characterized by impaired myocardial vasoreactivity.

Increased lipoprotein(a) is associated with reduced myocardial vasoreactivity in young healthy men

Objectives and Background: We examined the association between lipoprotein(a) and myocardial vasoreactivity in healthy men. Methods: Thirty non-smoking healthy men (age 34 ± 6 years) were studied: 9 had increased lipoprotein(a) (>200 mg/L) concentrations (lipoprotein(a) 317 (range 218–550) mg/L) and 21 had normal lipoprotein(a) (<200 mg/L) concentrations (lipoprotein(a) 57 (range 13–156) mg/ L). The myocardial blood flow measurements were performed basally and during adenosine infusion (140 μg/kg/min) with or without simultaneous physiological hyperinsulinemia (insulin infusion at a rate of 1 mU/kg/min) using positron emission tomography and [ 15O]H 2O. Results: Basal myocardial blood flow was similar between the subjects with increased and normal lipoprotein(a) (0.76 ± 0.20 and 0.79 ± 0.20 mL g −1 min −1, NS). Adenosine-stimulated flow tended to be reduced in subjects with increased lipoprotein(a) (3.1 ± 0.7 mL g −1 min −1 versus 3.7 ± 1.1 mL g −1 min −1, respectively, p = 0.1). During physiological hyperinsulinemia adenosine-stimulated flow was further enhanced in both groups but significantly blunted in subjects with increased lipoprotein(a) (3.7 ± 0.8 mL g −1 min −1 versus 4.8 ± 1.4 mL g −1 min −1, respectively, p = 0.03). This difference remained significant after simultaneous controlling for BMI, HbA1c, LDL-cholesterol, HDL-cholesterol and blood pressure ( p = 0.04). Conclusions: Already young healthy men with lipoprotein(a) concentrations greater than 200 mg/L are characterized by impaired myocardial vasoreactivity.

High serum leptin is associated with attenuated coronary vasoreactivity.

Hyperleptinemia, a hallmark of obesity, appears to be a risk factor for coronary artery disease. However, although leptin is a vasoactive hormone, no studies addressing leptin's effect on coronary perfusion have been performed. We examined the association between circulating leptin concentration and coronary vasoreactivity in young obese and nonobese males. Myocardial blood flow was quantitated in 10 obese men (age 31 +/- 7 years, BMI 34 +/- 2 kg/m(2)) and 10 healthy matched nonobese men (age 33 +/- 8 years, BMI 24 +/- 2 kg/m(2)) using positron emission tomography and O-15-water. The measurements were performed basally and during adenosine infusion (140 micro g/kg per minute). Serum leptin was significantly higher in obese than nonobese subjects (10.3 +/- 5.6 vs. 4.3 +/- 2.5 ng/mL, p < 0.01). Basal myocardial blood flow was not significantly different between obese and nonobese subjects. Adenosine-stimulated flow was blunted in obese (3.2 +/- 0.6 mL/g per minute) when compared with nonobese subjects (4.0 +/- 1.1 mL/g per minute, p < 0.05). Serum leptin concentration was inversely associated with adenosine-stimulated flow in study subjects (r = -0.50, p < 0.05). This association was no longer observed after adjustment for obesity and/or hyperinsulinemia. Hyperleptinemia and reduced coronary vasoreactivity occur concomitantly in young obese but otherwise healthy men. Moreover, the adenosine-stimulated myocardial flow is inversely related to prevailing concentration of serum leptin. Although this relationship appears to be explained by obesity and/or hyperinsulinemia, leptin might have a role in regulation of myocardial blood supply.

Independent association of type 2 diabetes and coronary artery disease with myocardial insulin resistance.

Clustering of classical cardiovascular risk factors is insufficient to account for the excess coronary artery disease (CAD) of patients with diabetes, and chronic hyperglycemia and insulin resistance (IR) are obvious culprits. Whole-body and skeletal muscle IR is characteristic of patients with type 2 diabetes, but whether it extends to the normally contracting cardiac muscle is controversial. We investigated whether type 2 diabetes is associated with myocardial IR independent of CAD in a case-control series (n = 55) of male nondiabetic and diabetic (type 2 and type 1) patients with or without angiographically documented CAD. Baseline blood flow ((15)O-water) and insulin-stimulated glucose uptake ((18)F-fluoro-deoxyglucose) during euglycemic (5.6 mmol/l), physiological hyperinsulinemia (40 mU x min(-1) x m(-2) insulin clamp) were measured by positron emission tomography in skeletal muscle and normally contracting myocardium. Skeletal muscle glucose uptake was reduced in association with both CAD and type 2 diabetes. In regions with normal baseline perfusion, insulin-mediated myocardial glucose uptake was reduced in non-CAD type 2 diabetic (0.36 +/- 0.14 micro mol x min(-1). g(-1)) and nondiabetic CAD patients (0.44 +/- 0.15 micro mol x min(- 1) x g(-1)) in comparison with healthy control subjects (0.61 +/- 0.08) or with non-CAD type 1 diabetic patients (0.80 +/- 0.13; P < 0.001 for both CAD and diabetes). Neither basal skeletal muscle nor basal myocardial blood flow differed across groups; both skeletal muscle and myocardial IR were directly related to whole-body IR. We conclude that type 2 diabetes is specifically associated with myocardial IR that is independent of and nonadditive with angiographic CAD and proportional to skeletal muscle and whole-body IR.

Obesity affects myocardial vasoreactivity and coronary flow response to insulin.

Obesity is associated with increased risk for cardiovascular diseases and peripheral endothelial dysfunction. We examined whether myocardial vasoreactivity and coronary-flow response to insulin stimulation are altered in obesity. Myocardial blood flow was quantitated in 10 obese men (body mass index, 33.6 +/- 1.9 kg/m(2)) and 10 healthy matched non-obese men (body mass index, 24.2 +/- 1.9 kg/m(2)), using positron emission tomography and oxygen-15-labeled water. The measurements were performed basally and during adenosine infusion (140 microg/kg per minute), with or without simultaneous physiological (1 mU/kg per minute) and supraphysiological (5 mU/kg per minute) hyperinsulinemia. Basal myocardial blood flow was not significantly different between obese and non-obese subjects. Adenosine-stimulated flow was blunted in obese (3.2 +/- 0.6 mL/g per minute) when compared with non-obese subjects (4.0 +/- 1.1 mL/g per minute, p < 0.05). Simultaneous physiological hyperinsulinemia increased adenosine-stimulated myocardial flow significantly in both groups (to 4.03 +/- 1.24 and 4.85 +/- 1.04 mL/g per minute in obese and non-obese men, respectively; p < 0.05 vs. adenosine). Supraphysiological hyperinsulinemia further enhanced the adenosine-stimulated flow in non-obese subjects (to 5.56 +/- 0.98 mL/g per minute; p < 0.05) but not in obese subjects. Young obese, healthy men have reduced myocardial vasoreactivity, which may represent an early precursor of future coronary artery disease. Additionally, insulin-induced enhancement of myocardial blood flow is blunted in obesity. Thus, endothelial dysfunction seems to also characterize myocardial vasculature of obese subjects.

Dose-dependent vasodilating effects of insulin on adenosine-stimulated myocardial blood flow.

In the peripheral vasculature, insulin induces time- and dose-dependent vasodilation. We have recently demonstrated that insulin potentiates adenosine-stimulated myocardial blood flow. However, it is unknown whether insulin's effects on the coronary vasculature are dose dependent. In this study, we quantitated myocardial blood flow and adenosine-stimulated coronary flow (140 microg.kg(-1).min(-1) for 5 min) in 10 healthy men (age, 32 +/- 6 years; BMI, 24.1 +/- 1.8 kg/m(2)) using positron emission tomography and (15)O-labeled water. Hyperemic myocardial blood flow was measured in the basal state, during euglycemic physiological hyperinsulinemia (serum insulin approximately 65 mU/l) and during supraphysiological hyperinsulinemia (serum insulin approximately 460 mU/l). Basal myocardial blood flow was 0.84 +/- 0.17 ml.g(-1).min(-1). Physiological hyperinsulinemia increased the adenosine-stimulated flow by 20% (from 3.92 +/- 1.17 to 4.72 +/- 0.96 ml.g(- 1).min(-1); P < 0.05). Supraphysiological hyperinsulinemia further enhanced the adenosine-stimulated flow by 19% (to 5.61 +/- 1.03 ml.g(-1).min(-1); P < 0.05). These effects were not explained by changes in systemic hemodynamics, since coronary resistance decreased during each insulin infusion (P < 0.05). In addition, hyperemic myocardial blood flow responses during insulin stimulation were positively correlated with whole-body glucose uptake. The results demonstrate that insulin is able to enhance hyperemic myocardial blood flow in a dose-dependent manner in healthy subjects. These effects might contribute to the known beneficial dose-dependent effects of insulin on myocardial ischemia.

Myocardial flow reserve in patients with a systemic right ventricle after atrial switch repair

OBJECTIVESThe purpose of this study was to assess myocardial blood flow (MBF) and flow reserve in systemic right ventricles (RV) in long-term survivors of the Mustard operation.BACKGROUNDThere is a high prevalence of systemic RV dysfunction and impaired exercise performance in long-term survivors of the Mustard operation. A mismatch between myocardial blood supply and systemic ventricular work demand has been proposed as a potential mechanism.METHODSWe assessed MBF at rest and during intravenous adenosine hyperemia in 11 long-term survivors of a Mustard repair (age 18 ± 5 years, median age at repair 0.7 years, follow-up after repair 17 ± 5 years) and 13 healthy control subjects (age 23 ± 7 years), using N-13 ammonia and positron emission tomography imaging.RESULTSThere was no difference in basal MBF between the systemic RV of survivors of the Mustard operation and the systemic left ventricle (LV) of healthy control subjects (0.80 ± 0.19 vs. 0.74 ± 0.15 ml/g/min, respectively, p = NS). However, the hyperemic flows were significantly lower in systemic RVs than they were in systemic LVs (2.34 ± 0.0.69 vs. 3.44 ± 0.62 ml/g/min respectively, p < 0.01). As a result, myocardial flow reserve was lower in systemic RVs than it was in systemic LVs (2.93 ± 0.63 vs. 4.74 ± 1.09, respectively, p < 0.01).CONCLUSIONSMyocardial flow reserve is impaired in systemic RVs in survivors of the Mustard operation. This may contribute to systemic ventricular dysfunction in these patients.

Evidence of reduced resting blood flow in viable myocardial regions with chronic asynergy

OBJECTIVESWe tested the hypothesis in patients (n = 24) with ischemic heart disease that chronic contractile dysfunction occurs in myocardial regions with true reduction in rest blood flow.BACKGROUNDWhether viable myocardial regions with chronic contractile dysfunction have true reduction in rest myocardial blood flow is controversial.METHODSPositron emission tomography (PET) 13N-ammonia was used to measure myocardial blood flow in combination with 18F-fluorodeoxyglucose (18FDG) to assess myocardial viability. Viability also was assessed by dobutamine echo and recovery of function after coronary artery bypass grafting (CABG). Segments (n = 252) were selected based on PET measured reduced resting blood flow and rest asynergy on echo.RESULTSRegional myocardial viability was present in 20 of 23 patients by PET, 13 of 23 by dobutamine echo and 10 of 11 by postrevascularization criteria. Rest blood flow in normal regions was 1.14 ± 0.52 ml/min/g and by definition exceeded (p < 0.005) that in both viable (0.48 ± 0.15; n = 8 patients) and nonviable (0.45 ± 0.14; n = 8 patients) regions (post-CABG criteria), which did not differ. Correction of rest myocardial blood flow in viable asynergic segments, only, for fibrosis and incomplete tracer recovery raised the level to 0.67 ± 0.21 (p < 0.005 vs. normal). Finally, evidence of both stunning (rest asynergy with normal flow) and hibernation was present in 15 of 23 (65%) patients.CONCLUSIONSReduced rest blood flow in viable myocardial regions with chronic asynergy is common and cannot be accounted for by partial volume effect. Thus, hypotheses concerning physiologic mechanisms underlying chronic contractile dysfunction should consider the role played by chronic reduction of basal myocardial blood flow.

Early alterations of myocardial blood flow reserve in heart transplant recipients with angiographically normal coronary arteries

Background: The evaluation of the coronary reserve provides valuable information on the status of coronary vessels. Therefore, we studied with positron emission tomography (PET) and 13N-ammonia the myocardial blood flow (MBF) reserve in heart transplant recipients free of allograft rejection and with angiographically normal coronary arteries early after heart transplantation (HTx). The MBF reserve was calculated as the ratio between MBF after dipyridamole injection and basal MBF normalized for the rate-pressure product. MethodsPatients were studied within 3 months (group A, n = 12) or more than 9 months (group B, n = 12) after HTx. Five patients have been studied both during the early and late period after HTx. Results were compared to those obtained in 7 normal volunteers (NL). ResultsGroup A recipients had a significantly lower dipyridamole MBF (in ml/min/100 gr of tissue) than that of group B recipients (142 ± 34 vs 195 ± 59, p < 0.05). This resulted in a significant decrease in MBF reserve early after HTx (group A: 1.82 ± 0.33) and a restoration to normal values thereafter (group B: 2.52 ± 0.53 vs NL: 2.62 ± 0.51, p = ns). Separate analysis of 5 patients studied twice is consistent with these results. ConclusionThis study shows that in heart transplant recipients free of allograft rejection and with normal coronary angiography, MBF reserve is impaired early after HTx. Restoration within one year suggests that this abnormality does not represent an early stage of cardiac allograft vasculopathy.

Pattern of changes over time in myocardial blood flow and microvascular dilator capacity in patients with normally functioning cardiac allografts

This study tests the hypothesis that myocardial blood flow and coronary microvascular dilator capacity vary as a function of time after orthotopic heart transplantation in humans. Positron emission tomography measurements of myocardial blood flow were obtained at rest and during adenosine in 24 patients between 1 and 86 months after heart transplantation. At the time of the study all patients were clinically well and had angiographically normal epicardial coronary artery vessels. Patients were divided into 3 groups based on time from transplant to positron emission tomography measurement of myocardial blood flow: group 1 to 12 months (n = 9); group 13 to 34 months (n = 8); and group ≥37 months (n = 7). Basal myocardial blood flow in group 1 to 12 months (1.86 ± 1.01 ml/min/g) exceeded (p <0.05) that of group 13 to 34 months (1.17 ± 0.73) and group ≥37 months (0.98 ± 0.34). In group 13 to 34 months, basal myocardial blood flow and maximal dilator capacity (minimal coronary vascular resistance with adenosine 36 ± 12 mm Hg/ml/min/g) were comparable to that of normal volunteers (1.01 ± 0.20 and 37 ± 9, respectively). In group ≥37 months, maximal flow response to adenosine was reduced (2.54 ± 1.25 vs 3.16 ± 0.52, respectively, p = 0.06). Maximal dilator capacity in group ≥37 months (60 ± 34) was impaired versus group 1 to 12 months (36 ± 10) and group 13 to 34 months (36 ± 12; both p <0.05) as well as normals (37 ± 9, p <0.05). During the first year after cardiac transplantation basal myocardial blood flow is elevated out of proportion to external determinants of myocardial oxygen demand, but maximal dilator capacity of the coronary microcirculation is normal. Between 1 and 3 years both basal myocardial blood flow and microvascular function tend to normalize. After 3 years, although basal myocardial blood flow is normal, microvascular dilator capacity is impaired.

Early impairment of coronary flow reserve in young men with borderline hypertension

Objectives. The purpose of this study was to investigate whether functional abnormalities in coronary vasomotion are present in young healthy asymptomatic men fulfilling the World Health Organization (WHO) criteria for borderline hypertension.Background. Previous studies have reported reduced coronary flow reserve in middle-aged subjects with sustained hypertension and hypertension-induced microvascular heart disease or left ventricular hypertrophy.Methods. Myocardial blood flow was measured at baseline and during dipyridamole-induced hyperemia by means of positron emission tomography and oxygen-15–labeled water in asymptomatic young men with borderline hypertension (group 1: n = 16, mean ± SD age 37 ± 4 years, 24-h ambulatory blood pressure 135 ± 10/81 ± 9 mm Hg) and matched healthy control subjects (group 2: n = 19, age 35 ± 3 years, 24-h ambulatory blood pressure 119 ± 8/69 ± 8 mm Hg, p < 0.001). Left ventricular (LV) mass, dimensions and function were measured by echocardiography.Results. LV mass, dimensions and diastolic function were similar in the study groups. Baseline myocardial blood flow was similar (0.83 ± 0.21 vs. 0.80 ± 0.22 ml/g per min, group 1 vs. group 2, respectively, p = NS), and a significant increase in flow was detected after dipyridamole infusion (0.56 mg/kg body weight in 4 min intravenously) in both groups. However, the flow response to dipyridamole was significantly lower in group 1, leading to lower hyperemic flow in group 1 than in group 2 (2.85 ± 1.20 vs. 3.80 ± 1.44 ml/g per min, respectively). Consequently, the coronary flow response was lower in hypertensive than in normotensive men (3.46 ± 1.23 vs. 4.99 ± 2.5 ml/g per min, group 1 vs. group 2, respectively, p < 0.05).Conclusions. These results demonstrate reduced coronary reactivity present in young asymptomatic men with borderline hypertension and no signs of hypertension-induced angina or left ventricular hypertrophy. Because baseline basal myocardial blood flow was unchanged, the reduction in coronary flow reserve depends on an impaired maximal vasodilator capacity.

Myocardial Flow Reserve in Long-Term Survivors of Repair of Anomalous Left Coronary Artery From Pulmonary Artery

Objectives. This study sought to evaluate regional myocardial flow reserve in long-term survivors of repair of anomalous left coronary artery from pulmonary artery (ALCAPA) and to relate the flow abnormalities to the patients’ exercise performance.Background. Patients with ALCAPA usually present during infancy with severe ischemic cardiomyopathy. The left ventricular function recovers after surgical repair. However, the extent of recovery of myocardial blood flow (MBF) and its potential physiologic significance in long-term survivors are unknown.Methods. We evaluated MBF (ml/g per min) at baseline and during maximal coronary vasodilation by adenosine in 11 patients after ALCAPA repair (median age 17 years, range 7 to 22) using nitrogen-13 ammonia and dynamic positron emission tomographic imaging. Patients also underwent an incremental exercise test with metabolic monitoring. In each patient, MBF was quantified in the three major vascular territories: the left anterior descending and left circumflex coronary artery territories and the right coronary artery (control region) territory.Results. Basal MBF was mildly reduced in the left coronary territories versus the control region (0.79 ± 0.14 vs. 0.85 ± 0.19, p = 0.05). During hyperemia, flow in the left coronary territories was significantly lower than that in the control region (2.1 ± 0.5 vs. 2.6 ± 0.5, p < 0.001). As a result, myocardial flow reserve was lower in the left coronary territories than in the control region (2.6 ± 0.7 vs. 3.2 ± 0.7, p < 0.001). Exercise performance was impaired in patients when compared with age-matched control subjects. Maximal oxygen consumption correlated linearly with maximal hyperemic flows in the left coronary artery territories (r = 0.73, p = 0.03).Conclusions. Long-term survivors of ALCAPA repair demonstrate regional impairment of myocardial flow reserve. This may contribute to impaired exercise performance by limiting cardiac output reserve.

Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution.

The myocardial perfusion reserve, defined as the ratio of hyperemic and basal myocardial blood flow, is a useful indicator of the functional significance of a coronary artery lesion. Rapid magnetic resonance (MR) imaging for the noninvasive detection of a bolus-injected contrast agent as a MR tracer is applied to the measurement of regional tissue perfusion during rest and hyperemia, in patients with microvascular dysfunction. A Fermi function model for the distribution of tracer residence times in the myocardium is used to fit the MR signal curves. The myocardial perfusion reserve is calculated from the impulse response amplitudes for rest and hyperemia. The assumptions of the model are tested with Monte Carlo simulations, using a multiple path, axially distributed mathematical model of blood tissue exchange, which allows for systematic variation of blood flow, vascular volume, and capillary permeability. For a contrast-to-noise ratio of 6:1, and over a range of flows from 0.5 to 4.0 ml/min per g of tissue, the ratio of the impulse response amplitudes for hyperemic and basal flows is linearly proportional to the ratio of model blood flows, if the mean transit time of the input function is shorter than approximately 9 s. The uncertainty in the blood flow reserve estimates grows both at low (< 1.0 ml/min/g) and high (> 3-4 ml/min/g) flows. The predictions of the Monte Carlo simulations agree with the results of MR first pass studies in patients without significant coronary artery lesions and microvascular dysfunction, where the perfusion reserve in the territory of the left anterior descending coronary artery (LAD) correlates linearly with the intracoronary Doppler ultrasound flow reserve in the LAD (r = 0.84), in agreement with previous PET studies.