Impact of Type 2 Diabetes on Nitric Oxide and Adrenergic Modulation of Myocardial Perfusion (original) (raw)
Related papers
Diabetes Care, 2020
OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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/...
Nitric oxide modulation of renal and cardiac hemodynamics in type 2 diabetes
European Journal of Endocrinology, 2002
Objective: To evaluate endothelial function in type 2 diabetic patients with and without diabetic nephropathy. Methods: We studied the effects of systemic infusion of the nitric oxide (NO) synthase inhibitor N Gmonomethyl-L-arginine (L-NMMA) on cardiovascular and renal hemodynamics in six type 2 diabetic patients with microalbuminuria (D2-MA), six type 2 diabetic patients with normoalbuminuria (D2-NA) and five control subjects. Both type 2 diabetic patients and control subjects had mild arterial hypertension. Results: L-NMMA infusion decreased the cardiac index in all groups. A reduction in glomerular filtration rate (GFR) and an increase in filtration fraction were observed only in controls. Renal plasma flow decreased in controls and D2-NA patients and renal vascular resistance increased in all groups. Conclusions: The effect of L-NMMA on cardiac output was similar in controls and type 2 diabetic patients with and without diabetic nephropathy. In contrast, the effect on GFR was impaired in both diabetic groups, suggesting that glomerular NO homeostasis is altered in type 2 diabetes. Moreover the discrepancy, in diabetic patients, between cardiac and renal effects during L-NMMA infusion suggests that the modulation of glomerular hemodynamics is independent from NO-regulated cardiac output.
4.499mTcN-DBODC: human biodistribution, dosimetry and safety of a new myocardial perfusion agent
Journal of Nuclear Cardiology, 2007
Background: Type 2 diabetic patients are characterized by a reduced adenosineinduced hyperemic myocardial perfusion (MP) which may contribute to their increased cardiovascular morbidity. We hypothesized that the reduced hyperemia can be explained by functional changes in endothelial or autonomic nervous regulation, since type 2 diabetes is associated with endothelial dysfunction and cardiac autonomic neuropathy. Methods and Results: In 12 type 2 diabetic patients with normal left ventricular ejection fraction and without signs of ischaemic heart disease and in 14 age-matched control subjects MP was measured at rest, during adenosine (MPado), and during adenosine and systemic ␣-receptor blockade with phentolamine using positron emission tomography on 2 separate days: 1) with, and 2) without systemic NO synthase (NOS) inhibition with NG-nitro-L-arginine methyl ester (L-NAME). MPado was lower in type 2 diabetic patients compared to control subjects (2.66Ϯ0.58 vs. 3.25Ϯ0.80 mL/g/min, Pϭ0.05). NOS inhibition abolished this difference (3.02Ϯ0.68 and 2.98Ϯ0.75 mL/g/ min, P NS). However, no significant effect of NOS inhibition on MPado was found in any of the groups (control subjects: 2.98Ϯ0.75 and 3.25Ϯ0.80 mL/g/min; type 2 diabetic patients: 3.02Ϯ0.68 and 2.66Ϯ0.58 mL/g/min, P NS in both groups). In type 2 diabetic patients, ␣-receptor blockade decreased MPado (2.19Ϯ0.61 vs. 2.66Ϯ0.58 mL/g/min, PϽ0.01) while no such effect was found in the control subjects (2.90Ϯ0.78 vs. 3.25Ϯ0.80 mL/g/min, P NS). When correcting for changes in mean arterial pressure (MAP) in the 2 groups using myocardial vascular resistance (MVR ϭ MAP / MP), no effect of ␣-receptor blockade was found in any of the groups (control subjects: 29Ϯ8 and 30Ϯ6 mmHg/mL/min/g; type 2 diabetic patients: 36Ϯ13 and 34Ϯ10 mmHg/mL/ min/g, P NS in both groups). After NOS inhibition ␣-receptor blockade had no effect on MPado in any of the groups. At rest, a significant correlation was observed between rate-pressure product and MP in control subjects (r²ϭ0.46, Pϭ0.007). NOS inhibition and type 2 diabetes abolished this correlation. Conclusion: Endothelial and cardiac autonomic nerve function seems to play only a minimal role in the reduced hyperemic myocardial perfusion in type 2 diabetic patients. However, the linear correlation between resting perfusion and cardiac work appears to be abolished in type 2 diabetic patients and during NO synthase inhibition.
Effect of Diabetic Autonomic Neuropathy on Determinants of Myocardial Oxygen Demand
2014
Background: Resting myocardial oxygen demand determinants are less studied in diabetic autonomic neuropathy patients. Objective: An insight into the determinants of myocardial oxygen demand in diabetic autonomic neuropathy patients may explain sudden adverse cardiovascular events in such patients. Methods: Case control study (n=60) was done on forty age matched (40-60 yr) type 2 diabetics with/ without diabetic cardiac autonomic neuropathy and twenty controls for myocardial oxygen demand determinants (heart rate, rate pressure product, systolic blood pressure) at rest. Results: Results demonstrated (unpaired't' – test, 'SPSS' software) that all variables were significantly increased in neuropathy patients compared to controls (p12) in neuropathy patients. Conclusion: Diabetic cardiac autonomic neuropathy significantly increases all determinants of resting myocardial oxygen demand contributing to exaggerated ischemic episodes and increased mortality even at rest.
Circulation, 2004
Background-Nitric oxide (NO) is an endothelial mediator that regulates vascular smooth muscle tone, but it may exert its cardiovascular action also by modulating the autonomic control of vasomotor tone. We assessed the effect of simultaneous inhibition of both endothelial (eNOS) and neuronal (nNOS) NO synthase isoforms on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers and in (denervated) transplant recipients. Methods and Results-MBF (mL · min Ϫ1 · g Ϫ1 ) was measured at rest and during adenosine-induced hyperemia with positron emission tomography and 15 O-labeled water. CFR was calculated as adenosine/resting MBF. Measurements were repeated during one of the following intravenous infusions: group 1 (nϭ12), saline; group 2 (nϭ9), 3 mg/kg N G -monomethyl-L-arginine (L-NMMA), which crosses the blood-brain barrier and inhibits both eNOS and nNOS; group 3 (nϭ13), 10 mg/kg L-NMMA; group 4 (nϭ8), phenylephrine titrated to simulate the hemodynamic changes in group 3; and group 5 (nϭ6), 10 mg/kg L-NMMA infused into the heart transplant recipients. After intervention, hyperemic MBF and CFR were unchanged in groups 1, 2, and 4. By contrast, both hyperemic MBF (ϩ53%, PϽ0.0001 versus baseline) and CFR (ϩ52%, PϽ0.0001 versus baseline) increased in group 3, whereas they remained unchanged in group 5, which suggests that an intact cardiac innervation was required for the increase in MBF and CFR observed in group 3.
CLINICAL STUDY Nitric oxide modulation of renal and cardiac hemodynamics in type 2 diabetes
2015
Objective: To evaluate endothelial function in type 2 diabetic patients with and without diabetic nephropathy. Methods: We studied the effects of systemic infusion of the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on cardiovascular and renal hemodynamics in six type 2 diabetic patients with microalbuminuria (D2-MA), six type 2 diabetic patients with normoalbuminuria (D2-NA) and five control subjects. Both type 2 diabetic patients and control subjects had mild arterial hypertension. Results: L-NMMA infusion decreased the cardiac index in all groups. A reduction in glomerular fil-tration rate (GFR) and an increase in filtration fraction were observed only in controls. Renal plasma flow decreased in controls and D2-NA patients and renal vascular resistance increased in all groups. Conclusions: The effect of L-NMMA on cardiac output was similar in controls and type 2 diabetic patients with and without diabetic nephropathy. In contrast, the effect on GFR was i...
Cardiac autonomic dysinnervation and myocardial blood flow in long-term Type 1 diabetic patients
Diabetic Medicine, 2003
The aim of the study was to assess scintigraphically the relationship between myocardial blood flow response and sympathetic dysinnervation in long-term Type 1 diabetic patients. Effects of the iron chelator deferoxamine on myocardial blood flow were studied and they were investigated according to the presence of cardiac sympathetic dysfunction. Methods Myocardial blood flow (MBF) was assessed with N-13 ammonia positron emission tomography in 13 long-term Type 1 diabetic patients and 13 control subjects at rest and in response to sympathetic stimulation (cold pressor test (CPT)). In diabetic patients, the study was repeated after preinfusion with deferoxamine. Furthermore, 123 I metaiodobenzylguanidine (MIBG) scintigraphy was applied to assess regional cardiac sympathetic dysinnervation (uptake score 1 = normal, homogeneous uptake … 6 = no uptake). Results In diabetic patients, MBF increased in response to CPT from 78 ± 18 ml /100 g /min to 84 ± 26 ml /100 g (8%, P < 0.001). Control subjects demonstrated an increase from 63 ± 17 ml /100 g to 84 ± 26 ml /100 g (33%, P < 0.001), respectively. Resting MBF was higher in diabetic patients than in control subjects (P < 0.001). In diabetic patients, increase in MBF in response to CPT was significant in regions with a MIBG uptake score of ≤ 3. Regions with a MIBG uptake score of > 3 did not exhibit a significant increase in MBF in response to CPT. After administration of deferoxamine, the increase in MBF in response to CPT was 23% and the magnitude of increase was related to the MIBG uptake score (r = 0.40, P < 0.0001). Conclusions Myocardial blood flow response to sympathetic stimulation is significantly impaired in long-term Type 1 diabetes. After preinfusion with deferoxamine the impairment is partially reversed and a relationship between myocardial blood flow and the extent of cardiac sympathetic dysfunction is observed.
European Heart Journal - Cardiovascular Imaging, 2019
Aims Coronary microvascular disease (CMD) is a known complication in type 2 diabetes mellitus (T2DM). We examined the relationship between diabetic complications, left ventricular (LV) function and structure and myocardial perfusion reserve (MPR) as indicators of CMD in patients with T2DM and control subjects. Methods and results This was a cross-sectional study of 193 patients with T2DM and 25 controls subjects. Patients were grouped as uncomplicated diabetes (n = 71) and diabetes with complications (albuminuria, retinopathy, and autonomic neuropathy). LV structure, function, adenosine stress, and rest myocardial perfusion were evaluated by cardiovascular magnetic resonance. Echocardiography was used to evaluate diastolic function. Patients with uncomplicated T2DM did not have significantly different LV mass and E/e* but decreased MPR (3.8 ± 1.0 vs. 5.1 ± 1.5, P < 0.05) compared with controls. T2DM patients with albuminuria and retinopathy had decreased MPR (albuminuria: 2.4 ± 0...
Autonomic influence on cardiovascular performance in diabetic subjects
The American Journal of Medicine, 1989
PURPOSF~ Cardiomyopathy, coronary artery atherescleresis, or autonomic neuropathy may affect the ~Lrdiovs~nlar performance of the diabetic pabent. To evaluate the role of parasympathetic nervons system activity on cardiovascular performance, 25 diabetic subjects who lacked symptoms, signs, or objective measurements of ischemla or cardiomyopathy were studied. PATIENTS AND METHODS: Diabetic subjects were classified according to their RR variation, an index of cardiac parasympathetic nervous system activity. Fourteen diabetic subjects had a normal RR variation of greater than 30 (D-NOR), and 11 diabetic patients had an abnormal RR variation of less than 20 (INABN). Fifteen age-and weightmatched, healthy, nondiabetic subjects (NOR) constituted the control group. All subjects had oxygen consumption, multigated acquisition determination of cardiac output, and work product measured before and during supine bicycle maYimum exercise testing. RESULTS: There was no difference in the resting cardiac output among the groups. Resting work product, however, was greatest in the D-ABN group when compared with performance in the other two groups (D-ABN: 11~500 4-800, D-NOtE 9,000 4-600, NOtE 8,700 4-400, p <0.0025). This was due to an increase in beth heart rate (p <0.025) and systolic blood pressure (p <0.015). In the diabetic subjects, there was an inverse relationship between the RR variation and resting work product (r = 0.47, n ffi 25, p <0.005). In response to exercise, the percent increase in cardiac output at matched percent ma~rlmum oxygen uptake was greatest in the NOR, D-NOR, and D-ABN groups, respectively (analysis of variRnce, p <0.01). In the diabetic subjects, there was a significant relationship between the RR variation and the ma~rlmuIn percent cha-ge in cardiac output (r = 0.41, n = 25, p <0.02). Compared with the NOR group, the mn~rimum increase in work product was impaired in diabetic subjects (p <0.002) and not different between the D-NOR and D-ABN groups. CONCLUSION~ The increase in resting work product and the poor cardiac output responses to exercise in the D-ABN group are due to a decrease in