Cerebrovascular reactivity in hypertensive patients: a transcranial Doppler study

PURPOSE: We studied the usefulness of transcranial Doppler sonography for assessing changes in vasoreactivity in patients with hypertension and the hemodynamic consequences of hypertension. METHODS: The study group comprised 25 patients with chronic severe hypertension and 25 age- and sex-matched healthy subjects. Cerebrovascular reserve capacity was assessed by transcranial Doppler recording of the blood flow velocity in both middle cerebral arteries before and 5, 10, 15, and 20 minutes after intravenous injection of 1 g of acetazolamide (Diamox). Blood pressure, blood gases, and other blood parameters were also measured before and after acetazolamide injection. The sizes of the left atrium, left ventricle, and aortic root were measured by echocardiography and correlated with the vasoreactivity after acetazolamide injection. RESULTS: After acetazolamide injection, no significant changes in blood pressure were observed in either group. The mean blood flow velocity in the middle cerebral arteries of hypertensive patients (60.8 +/- 2.6 cm/sec) was not significantly different from that of controls (58.8 +/- 1.9 cm/sec) before acetazolamide injection. Ten minutes after acetazolamide injection, the percentage change in blood flow velocity was significantly lower in the hypertensive group (36.2 +/- 4.5%) than in the controls (52.6 +/- 3.7%). A significant negative correlation (p < 0.05) between decreased vasoreactivity and increased size of the left atrium and aortic root was observed. CONCLUSIONS: Vasoreactivity decreases in hypertensive patients without neurologic deficits or computed tomography abnormalities. Enlargement of the left atrium correlates well with the severity of the impairment in vasoreactivity. Transcranial Doppler sonography can be a sensitive tool in the investigation of vascular impairment caused by hypertension and in the follow-up of hypertensive patients.     

Vasoreactive effect of acetazolamide as a function of time with sequential PET 15O-water measurement

The accurate assessment of vascular flow reserve is crucial for the evaluation of risk among patients with cerebrovascular disease. In six patients with unilateral occlusion of the internal carotid artery and one patient with unilateral occlusion of the middle cerebral artery (mean +/- S.D. age = 68 +/- 3 years), we measured cerebral blood flow (CBF) after the administration of 940 MBq 15O-water using a remotely controlled power injector. Studies were performed at rest, after 10 min, and then 10, 20 and 30 min after the administration of 1 mg acetazolamide to evaluate the vasoreactive effect, as reflected by an increase in CBF. Sixteen regions of interest (ROIs) were drawn over the CBF images. These ROIs were as follows in each hemisphere: Area I, four areas in the cortical middle cerebral arterial territory (superior frontal, frontal, temporal and parietal areas); Area II, four areas of the deep middle cerebral and vertebral arterial territory (occipital area, basal ganglia, thalamus and cerebellum). Taking normalized resting CBF to be 100%, the mean CBF measured 10, 20 and 30 min post-injection using sequential positron emission tomography was as follows: Area I, 141.4 +/- 16.3, 127.7 +/- 15.3 and 128.2 +/- 17.4% for non-occluded sites and 116.3 +/- 22.8, 112.7 +/- 16.4 and 114.9 +/- 17.1% for occluded sites; Area II, 143.4 +/- 14.5, 126.2 +/- 10.4 and 125.0 +/- 12.9% for non-occluded sites and 141.9 +/- 28.9, 126.0 +/- 20.5 and 124.1 +/- 17.1% for occluded sites. A significant difference in mean CBF was noted between the non-occluded and occluded sites in Area I, the most marked difference of 25.1% being observed 10 min after the administration of the acetazolamide. We conclude that for an accurate assessment of vascular reserve in patients with cerebrovascular disease, CBF should be measured 10 min post-administration of the acetazolamide.     

Cerebral hemodynamic changes in sleep apnea syndrome and effect of continuous positive airway pressure treatment

BACKGROUND AND OBJECTIVE: A clear association among snoring, sleep apnea, and increased risk of stroke has been shown by previous studies. However, the possible role played by sleep apnea in the pathogenesis of cerebrovascular disease is subject to debate. To evaluate the influence of hemodynamic changes caused by obstructive sleep apnea syndrome (OSAS), we investigated cerebrovascular reactivity to hypercapnia in patients with OSAS. METHODS: The study was performed at baseline and after 1 night and 1 month of nasal continuous positive airway pressure (n-CPAP) therapy, with patients in the waking state (8:00 to 8:30 AM and 5:30 to 6:00 PM) with transcranial Doppler ultrasonography. Cerebrovascular reactivity was calculated with the breath-holding index (BHI). RESULTS: In the baseline condition, compared with normal subjects, patients with OSAS showed significantly lower BHI values in both the morning (0.57 versus 1.40, p < 0.0001) and the afternoon (1.0 versus 1.51, p < 0.0001). Cerebrovascular reactivity was significantly higher in the afternoon than it was in the morning in both patients (p < 0.0001) and controls (p < 0.05). In patients, the BHI returned to normal values, comparable with those of control subjects, after both 1 night and 1 month of n-CPAP therapy. CONCLUSIONS: These findings suggest an association between OSAS and diminished cerebral vasodilator reserve. This condition may be related to the increased susceptibility to cerebral ischemia in patients with OSAS, particularly evident in the early morning.     

Cerebrovascular reactivity in non-insulin dependent diabetes mellitus (preliminary results)

AIMS: Previously numerous investigators reported about impairment of cerebrovascular reserve capacity in Type I, diabetes mellitus. However, no similar data are available about patients suffering from Type II diabetes. The goal of the study was to assess cerebrovascular reserve in Type II diabetic patients. PATIENTS AND METHODS: 14 NIDDM patients and 20 healthy controls were studied. Middle cerebral artery mean blood flow velocity was measured at rest and during 20 minutes after i.v. administration of 1 g. acetazolamide. Velocities measured after acetazolamide were compared to resting values and were expressed as the percent increase of the mean velocity. Data obtained in diabetics and healthy persons were compared using Student's t-test. The correlation between age of the patients, diabetes duration, actual blood glucose-, insulin-, glycosylated hemoglobin-, urine microalbumin concentrations and resting blood flow velocity and cerebrovascular reserve capacity was assessed using linear regression analysis. RESULTS: Resting cerebral blood flow velocities, cerebrovascular reactivity and reserve capacity did not differ from that of healthy controls. No correlation has been found between obtained laboratory parameters and resting cerebral blood flow velocities and cerebrovascular reserve capacity. CONCLUSIONS: Vasodilatory ability of the cerebral arterioles in NIDDM-patients did not differ from that of healthy control persons. Further studies are needed to find out an accurate screening method for detection of cerebral microangiopathic changes in Type II diabetes mellitus.     

Cerebrovascular reserve capacity many years after vasospasm due to aneurysmal subarachnoid hemorrhage. A transcranial Doppler study with acetazolamide test

BACKGROUND AND PURPOSE: Vasospasm in aneurysmal subarachnoid hemorrhage results in proliferative vasculopathy. Systemic hypertension also causes vascular hypertrophy. Both of these histological changes can lead to rigidity of the cerebrovascular system, reducing its autoregulatory capacity. METHODS: Blood flow velocity (BFV) in the middle cerebral artery at rest and cerebrovascular reserve capacity (CVRC) (percent rise in BFV after acetazolamide stimulation) measured by means of transcranial Doppler sonography were studied many years after aneurysmal subarachnoid hemorrhage in patients with proven cerebral vasospasm (mean BFV > 160 cm/s). The BFV under resting conditions and the CVRC values of the ipsilateral and the contralateral hemispheres were measured in 29 patients (mean age, 43 years; mean follow-up, 4.6 years) and compared with those of control subjects. RESULTS: Persistent high BFV (> 120 cm/s) was found in three patients in the peripheral branch of the ipsilateral middle cerebral artery. In the main trunks of the arteries of the anterior circle of Willis, BFV was normal in all cases. CVRC was normal in all patients (ipsilateral, 52 +/- 21%; contralateral, 56 +/- 17%); values did not differ significantly from each other or from the control value (45 +/- 18%). The higher value of CVRC on the contralateral side was found to be statistically significant in selected groups (hypertensive patients and patients with residual infarct on late CT). CONCLUSIONS: Proliferative vasculopathy developed at the time of vasospasm must have resolved and did not reduce late vasoreactivity. Comorbidity with hypertension also did not seem to influence the late vasoreactivity toward normalization.     

Is impaired cerebral vasomotor reactivity a predictive factor of stroke in asymptomatic patients?

BACKGROUND AND PURPOSE: Identification of the subgroup of asymptomatic patients with severe internal carotid artery stenosis and high risk of stroke has important clinical implications. Cerebral vasomotor reactivity provides information regarding intracranial hemodynamic features and might have a prognostic value in predicting cerebrovascular ischemic events, especially in patients with carotid stenosis. The aim of our study was to assess the cerebral vasomotor reactivity in asymptomatic patients with carotid stenosis and evaluate its role in stroke occurrence. METHODS: Cerebral vasomotor reactivity was assessed using transcranial Doppler ultrasonology and the Diamox test (intravenous administration of 1.0 g acetazolamide) in 44 asymptomatic patients with severe (> 70%) internal carotid artery stenosis. Patients were followed up prospectively (mean, 2 years). RESULTS: Cerebral vasomotor reactivity was estimated as good (> 40% increase of blood flow velocity in the middle cerebral artery ipsilateral to the carotid stenosis after undergoing the Diamox test) in 23 patients; it was impaired in the other 21. During the follow-up period, the overall annual rate for ipsilateral stokes was 2.3%; it was 7.9% for all ischemic cerebral events. No strokes or transient ischemic attacks occurred in the former group, but there were 7 cerebral ischemic events (2 strokes [1 fatal] and 5 transient ischemic attacks) in the latter group. There was a statistically significant correlation between cerebral ischemic events and impaired cerebral vasomotor reactivity (P = .009). CONCLUSIONS: The data of this preliminary study suggest an important role of impaired cerebral vasomotor reactivity in predicting ischemic cerebral events. Preventive vascular surgery might be considered in this high-risk subgroup of asymptomatic patients with severe carotid stenosis.     

Age and sex differences in cerebral hemodynamics: a transcranial Doppler study

BACKGROUND AND PURPOSE: Hemodynamic factors seem to play an important role in the pathogenesis of cerebral ischemic events. The aim of this study was to evaluate whether changes in cerebrovascular reactivity occur in women after menopause. METHODS: Using transcranial Doppler ultrasonography, we studied the changes of flow velocity after hypercapnia in the middle cerebral arteries of 45 healthy premenopausal women (mean age, 32.3 years; range, 20 to 47 years) and 40 postmenopausal women (mean age, 54.4 years; range, 48 to 64 years). The same measurements were recorded in two groups of healthy male subjects age matched with premenopausal (45 subjects) and postmenopausal women (40 subjects). Moreover, a subgroup of postmenopausal women aged 48 to 53 years (15 subjects) were compared with a group of 15 premenopausal women of the same age. We obtained hypercapnia with breath holding and evaluated cerebrovascular reactivity with the breath-holding index (BHI). RESULTS: BHI was significantly lower in postmenopausal women (0.89+/-0.3) than in premenopausal women (1.59+/-0.3; P<0.0001) and in young (1.34+/-0.5; P<0.001) and old men (1.20+/-0.4; P<0.04). In the latter group, BHI was significantly lower than in premenopausal women (P<.0001). BHI values were also significantly lower in postmenopausal than in premenopausal women of the same age (0.81+/-0.1 versus 1.34+/-0.1; P<0.0001). CONCLUSIONS: These findings suggest that the large reduction of cerebrovascular reactivity in postmenopausal women cannot be considered a simple factor related to aging but is probably influenced by hormonal changes. The alteration in cerebrovascular regulation could be involved in the increase of cerebrovascular disease in postmenopausal women.     

Increased fraction of circulating activated platelets in acute and previous cerebrovascular ischemia

Determination of circulating activated platelets may be helpful to estimate the prognosis and to stratify therapies in arterial vascular disorders including stroke. We used flow cytometry and phase contrast microscopy to study whether the fraction of platelets expressing p-selectin and CD63 and the fraction of platelets with shape change are increased in patients with acute and previous cerebrovascular ischemia. The proportion of platelets expressing activation dependent antigens was higher in patients with acute (n = 24; p-selectin: 8.23 +/- 4.21%; CD63: 3.53 +/- 2.53%) and with previous cerebrovascular ischemia (n = 46; 3.86 +/- 1.98%; 2.80 +/- 1.79%) as compared to age- and sex-matched control subjects (n = 35; 2.17 +/- 0.96%; 1.79 +/- 0.75%; p < or = 0.005, respectively). In patients with previous ischemia, there was no difference between treatment with aspirin (n = 25) or phenprocoumon (n = 21). Hypertension, diabetes mellitus and smoking were not associated with increased antigen expression (analysis of variance). The fraction of discoid platelets and platelet counts were not significantly different between groups. Our results indicate increased expression of platelet neoantigens in acute and to a less degree in previous cerebrovascular ischemia. Ongoing platelet activation after cerebrovascular ischemia despite therapy with aspirin or phenprocoumon indicates that new anti-platelet drugs may be of benefit for these patients. Flow cytometry appears to be a useful tool to assess platelet function in cerebrovascular ischemia.     

Diastolic dysfunction in patients with chronic kidney failure on a hemodialysis program

OBJECTIVE: The aim of this study was to analyse different ultrasound parameters for the assessment of isolated left ventricular diastolic dysfunction (LVDD) in patients with chronic renal failure (CRF) on periodic hemodialysis (HD), comparing pulsed wave Doppler with pulsed tissue Doppler. MATERIALS AND METHODS: Forty-seven patients with CRF on HD (61% were male; mean age was 51.0 +/- 16.5 years, mean HD time--3.7 +/- 3.8 years, 38% had hypertension, 17% had diabetes) were studied by echocardiography (bidimensional, M-Mode, flow pulsed Doppler and tissue Doppler imaging). All patients had symptoms of left heart failure-class II NYHA, were in sinus rhythm and had no symptoms of ischemic heart disease. The presence of abnormal LV regional contractility was the exclusion criteria. According to their mitral inflow profile Doppler characteristics, patients were included in two groups: Group A (E/A > 1; n = 21) and B (E/A < 1; n = 26). We compared: LV dimensions and function, left atrial (LA) dimension. Gaasch index, LV mass index. E and A wave velocities (in flow pulsatile Doppler and tissue Doppler). E/N ratio in tissue Doppler, isovolumetric relaxation time (IVRT) and deceleration time (DT). RESULTS: There were no significant differences in the prevalence of age > or = 65 years male sex, hypertension or diabetes between group A and B patients, and almost all patients were on hemodialytic treatment for more than one year (81% vs 85%: NS). LV hypertrophy was present in almost all group A and B patients (A--95% vs B--85.5%; NS). Group A, compared with group B, had a difference in the Gaasch index (2.45 +/- 0.3 vs 2.08 +/- 0.4; p < 0.05), E wave velocity in flow pulsatile Doppler and tissue Doppler (cm/sec) (110 +/- 27 vs 62 +/- 20; p < 0.001 and 41 +/- 15 vs 28.5 +/- 16; p < 0.05), E/A ratio in tissue Doppler (1.3 +/- 0.4 vs 0.8 +/- 0.3; p < 0.001). IVRT (msec) (80.7 +/- 15.2 vs 113.5 +/- 28.3; p < 0.001) and DT (msec) (189.7 +/- 24 vs 278.2 +/- 17.9; p < 0.001). According to the E'/A' ratio in tissue Doppler, group A patients were divided in another two groups: E'/A' > 1 (13/21--62%) and < 1 (8/21--38%) and a significantly longer IVRT (75.8 +/- 9.3 vs 100.9 +/- 3.2; p < 0.001) and DT (178 +/- 15 vs 240 +/- 20; p < 0.001) and a greater LA dimension (37.6 +/- 6.9 vs 44.6 +/- 6.9; p < 0.05) were found. CONCLUSIONS: Pulsed wave Doppler is the most useful non invasive method for assessment of global diastolic dysfunction. In our study, 17% of the patients had E/A < 1 only in the tissue Doppler study. These patients probably had a pseudonormal mitral pattern.     

Similar rate of progression in the predialysis phase in type I and type II diabetes mellitus

Progression of diabetic nephropathy from the stage of macroproteinuria with near-normal renal function until start of dialysis was compared in 16 patients with type I and 16 patients with type II diabetes mellitus. The mean creatinine clearance at the beginning of the study was 89 +/- 13 ml/min/1.73 m2 in patients with type I and 81 +/- 6 ml/min/1.73 m2 in those with type II diabetes. Dialysis was started after a mean interval of 77 (44-133) months, when creatinine clearance had decreased to 8 +/- 2 ml/min/1.73 m2 in type I diabetic patients. The respective figures for type II diabetic patients were 81 (40-124) months and 7 +/- 2 ml/min/1.73 m2. The mean rate of decrease in creatinine clearance was 1.05 +/- 0.45 ml/min/month in type I and 0.91 +/- 0.41 ml/min/month in type II diabetes. The mean rate of decrease was 1.46 +/- 0.30 ml/min/month in type I diabetic patients with a systolic BP > 160 mmHg versus 0.80 +/- 0.42 ml/min/month with < 160 mmHg (P < 0.01). In the type II diabetics the respective figures were 1.38 +/- 0.40 ml/min/month versus 0.78 +/- 0.15 ml/min/month (P < 0.01). During the observation period the prevalence of coronary heart disease increased from 6 to 50% in type I and from 31 to 87% in type II diabetes. In conclusion, the rate of progression of diabetic nephropathy during the predialytic phase is similar in type I and type II diabetes; BP adversely affects the rate of progression to the same extent in both groups.     

Multiplane transesophageal echocardiographic doppler imaging accurately determines cardiac output measurements in critically ill patients

OBJECTIVES: To compare cardiac output and stroke volume measured by multiplane transesophageal Doppler echocardiography with that measured by the thermodilution technique. DESIGN: Prospective direct comparison of paired measurements by both techniques in each patient. SETTING: Cardiac surgery and myocardial infarction intensive care units. PATIENTS: Twenty-nine patients, mean age (+/- SD) 67 +/- 8 years. Nineteen had undergone open heart surgery and 10 had suffered acute myocardial infarction. METHODS: Cardiac output and stroke volume were measured simultaneously by the thermodilution technique and multiplane transesophageal Doppler echocardiography via the transgastric view (119 +/- 8 degrees) with the sample volume positioned at the level of the left ventricular outflow tract. RESULTS: Stroke volume and cardiac output measurements were obtained in 29 of 33 patients (88%). Mean values were 50 +/- 13 mL and 4.8 +/- 1.3 L/min by Doppler and 51 +/- 14 mL and 4.9 +/- 1.4 L/min by thermodilution (r = 0.90, r = 0.91, p < 0.001). The mean differences in values obtained with the two techniques were 1 +/- 6 mL (2 +/- 12%) and 0.1 +/- 0.7 L/min (2 +/- 12%). CONCLUSIONS: Multiplane transesophageal echocardiography enhances the ability to estimate accurately cardiac output and stroke volume by providing new access to left ventricular outflow tract in critically ill patients.     

Cellular Ca2+ ATPase activity in diabetes mellitus

Basal and maximal Ca2+ ATPase activity was studied in erythrocytes of 29 healthy controls, 15 patients with insulin-dependent diabetes mellitus (IDDM) and 22 patients with non-insulin-dependent diabetes mellitus (NIDDM). Basal and maximal Ca2+ ATPase activity was significantly decreased in insulin-dependent diabetes mellitus (8.4 +/- 0.5 and 22.5 +/- 1.1 pmol/10(6) RBC/min) and non-insulin-dependent diabetes mellitus (7.3 +/- 1.0 and 18.6 +/- 1.8 pmol/10(6) RBC/min) compared to healthy controls (9.3 +/- 1.0 and 24.6 +/- 1.1 pmol/10(6) RBC/min). Maximal Ca2+ ATPase activity showed a significant correlation to systolic blood pressure in both insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus. There was no significant correlation of maximal Ca2+ ATPase activity to fasting serum glucose concentration and to HbA1 levels. Maximal Ca2+ ATPase activity was significantly correlated to creatinine clearance in non-insulin-dependent diabetes mellitus, but not in insulin-dependent diabetes mellitus. It is concluded that a decreased cellular Ca2+ ATPase activity may predispose to the development of hypertension in diabetes mellitus.     

A modified technic for local rt-PA catheter-mediated lysis

PURPOSE: To develop an economic and efficient concept for more time-saving local rt-PA thrombolysis therapy. METHOD: 40 patients with peripheral vascular occlusive disease stage IIb-III according to the Fontaine classification and with angiographically proven occluded segments of pelvic and lower limb arteries were treated by a modified concept of local rt-PA catheter thrombolysis. Via a thin guide wire the catheter for thrombolysis is slowly advanced through the thrombus without fluoroscopic control, outside the room in which angiography is performed. In 24 cases a short-term lysis and in 16 cases a long-term lysis was carried out. RESULTS: The initial success rate was 75%, the patency rate in six months' follow-up was 66.7%. The ankle-brachial index decreased from 0.4 +/- 0.3 to 0.8 +/- 0.2 on the average. There were no relevant clinical complications. The average occupancy time of the angiography room or table was 60 +/- 52 min, the average time of fluoroscopy was 17 +/- 13 min. CONCLUSION: In modified local rt-PA thrombolysis, short-term lysis and long-term lysis were mostly performed outside the angiography room, so that the exposure to radiation and there fore the radiation dose were reduced for both the patient and the attending staff. The angiography room is thus available for other patients and can therefore be used more efficiently.     

Effect of coat on rate of temperature increase in muscle during ultrasound treatment of dogs

BACKGROUND AND PURPOSE: The vasomotor response can be tested by means of transcranial Doppler sonography. If a constant vessel diameter is assumed, the flow velocity changes will reflect blood flow volume changes. This hypothesis is difficult to verify. Simultaneous assessment of intracranial flow velocity and extracranial flow volume changes may solve this problem. METHODS: We tested vasomotor response in 32 volunteers (age, 42+/-18 years) with 5% CO2. Acetazolamide (1 g) was tested in 15 volunteers (age, 28+/-8 years). To evaluate drug-dependent flow changes in the external carotid artery territory, acetazolamide was administered in 7 patients with unilateral occlusion of the internal carotid artery without evidence of collateralization through the ophthalmic artery (age, 67+/-12 years). Simultaneous recording included measurements of flow volume in the common carotid arteries (M-mode color duplex system) and flow velocity in the middle cerebral arteries. RESULTS: With CO2 and acetazolamide, intracranial flow velocity increased by 31% and 39%, respectively, with a simultaneous increase of common carotid artery flow volume of 47% and 50%, respectively. No change in extracranial flow volume was observed in patients with an occluded internal carotid artery. CONCLUSIONS: These data show not only the expected increase of flow velocity in the middle cerebral artery but also suggest an increase in cross-sectional vessel diameter of 6% and 4% with CO2 and acetazolamide, respectively. It remains unresolved whether this observation is due to a direct effect of the drug on the vessel walls or is simply pressure dependent.     

The dental, craniofacial, and biochemical features of pyknodysostosis: a report of three new cases

1.Near-infrared (IR) spectroscopy is based on the relative transparency of skin, skull and brain to the light in the near-IR region (700-1100 nm) and on the oxygen-dependent tissue absorption changes of haemoglobin.2. We evaluated the most relevant factors (reproducibility, venous return, age and sex) that might affect reliability of near-IR spectroscopy to test CO2 cerebrovascular reactivity.3.Thirty-four healthy volunteers were enrolled in the study. The protocol consisted of a 3-min baseline, a 3-min hypercapnia (5% CO2 in air) and a 2-min recovery. Transcranial Doppler sonography measurements were simultaneously performed. The CO2 reactivity test was repeated on 27 subjects after 1 h to assess reproducibility. CO2 reactivity was also evaluated at different body positions (supine, 35 degrees Trendelenburg and 35 degrees reverse Trendelenburg), and over a gradual increase of the inspired CO2.4. Changes in near-IR spectroscopy and transcranial Doppler sonography parameters were significantly correlated with variations of end-tidal CO2 (P<0.005). A significant correlation between the reactivity indexes of near-IR spectroscopy parameters and flow velocity was also found (P<0.01). A high reproducibility was also found for deoxyhaemoglobin (rI=0.76), oxyhaemoglobin (rI=0.68) and flow velocity (rI=0.60) reactivity indexes. No significant differences between the reactivity indexes of different body positions were found (P>0.05). The reactivity index of oxyhaemoglobin and deoxyhaemoglobin decreased (P<0.05) and increased (P<0.01) with age respectively.5. We found that near-IR spectroscopy is a reliable and reproducible method for the evaluation of cerebrovascular reactivity and might be considered, after appropriate validation, for the assessment of patients with cerebrovascular disease.     

Role of nitric oxide in coronary arterial vasomotion and the influence of coronary atherosclerosis and its risks

Healthy coronary vascular endothelium releases nitric oxide to modulate resting and dynamic coronary arterial tone. We studied the impact of atherosclerosis and/or its risks on endothelial nitric oxide release in response to metabolic stimuli by evaluating coronary vasomotor responses to atrial pacing before and after the inhibition of nitric oxide production by intracoronary NG-monomethyl-L-arginine (L-NMMA) (20 micromol/min) infusion. The study includes 34 patients (15 with coronary disease, 11 with normal coronary arteries and > or =1 risk factor, and 8 with normal coronary arteries and no risks). Coronary blood flow was derived from Doppler flow velocity (0.018-inch Doppler wire) and coronary diameter. L-NMMA infusion reduced coronary blood flow by 18 +/- 16% and coronary diameter by 10 +/- 9%. Responses were identical in all subgroups. Coronary blood flow responses to pacing were similar in all subgroups and were unaffected by L-NMMA (11 +/- 11 vs 13 +/- 9 ml/min; p = 0.26). Epicardial coronary vasodilation to control pacing occurred in patients with normal coronary arteries with (4.0 +/- 5.2%, p = 0.01) or without (8.0 +/- 5.2%, p = 0.03) risks, but not in patients with coronary disease (2.8 +/- 5.9%). L-NMMA abolished pacing-induced epicardial vasodilation in patients without coronary artery disease, producing a 1.8 +/- 5.1% response, which was similar in all subgroups. We conclude that microvascular responses to rapid atrial pacing are not mediated by nitric oxide. Flow-mediated epicardial coronary arterial responses may be nitric oxide dependent.     

Acetazolamide challenge and technetium-99m-ECD versus iodine-123-IMP SPECT in chronic occlusive cerebrovascular disease

We compared the acetazolamide challenge test using 99mTc-ECD SPECT and 123I-IMP SPECT images in patients with chronic occlusive cerebrovascular disease. We also evaluated the usefulness of linearization correction for acetazolamide challenge test of 99mTc-ECD SPECT. METHODS: Twenty patients with unilateral chronic occlusive cerebrovascular disease (10 patients had middle cerebral arterial lesion and 10 had internal carotid lesion) were included in the study. Split-dose (a dose fractioning was 1:2), and sequential SPECT technique was used for 99mTc-ECD SPECT studies while only acetazolamide challenge test studies for 123I-IMP SPECT were performed. Permeability surface area product model (PS model) and back-diffusion model (Lassen's correction) were used for linearization correction of acetazolamide challenge with 99mTc-ECD SPECT. RESULTS: Six of 16 patients with reduced vasodilatory capacity in 123I-IMP SPECT were underestimated by 99mTc-ECD SPECT acetazolamide challenge test. Relative ECD uptake normalized by cerebellar uptake compared with IMP uptake showed a nonlinear relationship, indicating relatively less uptake in high flow range. The underestimations of limited vasodilatory capacity observed in 99mTc-ECD SPECT without linearization correction was modified by linearization algorithm. However, the effect of correction based on PS model was superior than that of Lassen's correction. The corrected 99mTc-ECD uptake ratio, based on PS model, and IMP uptake ratio demonstrated a better linear relationship than that of Lassen's correction. CONCLUSION: Technetium-99m ECD SPECT corrected based on the PS model is a better method of linearization for evaluating cerebrovascular reserve using acetazolamide challenge.     

Changes in cerebral perfusion pressure in puerperal women with preeclampsia

OBJECTIVE: To determine the variation in the estimated maternal cerebral perfusion and cerebrovascular resistance (the resistance area product) in the puerperium. METHODS: The maternal middle cerebral artery was evaluated by transcranial Doppler ultrasound in ten women 2 days before labor, in 21 women in early labor and at 24 and 48 hours postpartum, and in 6 women at 1 week postpartum. Cerebral blood flow velocities were determined. Women were diagnosed initially with mild preeclampsia. Estimated cerebral perfusion pressure was Vmean/[Vmean - Vdiastolic] [BPmean - BPdiastolic]. Because the diameter of the vessels could not be measured directly, an index of resistance was calculated: the resistance area product = BPmean/velocitymean. We calculated an index of cerebral blood flow to be estimated cerebral perfusion pressure divided by resistance area product. Our study had a power of 80% to detect a 16-cm/second increase in middle cerebral blood flow velocity. RESULTS: Estimated maternal cerebral perfusion was maintained for up to 1 week postpartum. Cerebrovascular resistance did not change in the puerperium. Cerebral blood flow index (+/-standard deviation) was significantly increased at 1 week postpartum compared with early labor levels (28.3 +/-6.9 versus 46.7+/-15.6, respectively) (P < .05). CONCLUSION: Cerebral blood flow 1 week postpartum increased significantly over early labor values. These persistent changes in the cerebral vasculature might put patients at risk for seizures up to 1 week postpartum.     

Alterations in non-insulin-mediated glucose uptake in the elderly patient with diabetes

It is increasingly recognized that alterations in non-insulin-mediated glucose uptake (NIMGU) play an important pathogenic role in disorders of carbohydrate metabolism. This study was conducted to determine whether NIMGU is impaired in elderly patients with type 2 diabetes. Healthy elderly control subjects (n = 19, age 76 +/- 1 years, BMI 26.8 +/- 1.1 kg/m2) and elderly patients with type 2 diabetes (n = 19, age 76 +/- 2 years, BMI 27.5 +/- 0.9 kg/m2) underwent a 240-min glucose clamp study. Octreotide was infused to suppress endogenous insulin release, and tritiated glucose methodology was used to measure glucose uptake and disposal rates. For the first 180 min, glucose was kept at fasting levels. From 180 to 240 min, glucose was increased to 11 mmol/l. At fasting glucose levels, glucose uptake was similar in both groups. However, glucose clearance was reduced in patients with diabetes (control 1.68 +/- 0.05 ml x kg(-1) x min(-1); diabetes 1.34 +/- 0.07 ml x kg(-1) x min(-1), P < 0.0001). During hyperglycemia, glucose uptake was reduced in patients with diabetes (control 3.16 +/- 0.09 mg x kg(-1) x min(-1); diabetes 2.57 +/- 0.11 mg x kg(-1) x min(-1), P < 0.0001). Peripheral glucose effectiveness (SG) was less in patients with diabetes (control 1.28 +/- 0.04 ml x kg(-1) x min(-1); diabetes 0.94 +/- 0.08 ml x kg(-1) x min(-1), P < 0.0001). Hepatic glucose output and hepatic SG were not different between groups. We conclude that the effect of glucose on glucose uptake is impaired in elderly patients with type 2 diabetes, a finding that may have therapeutic implications for this patient population.     

Changes in cerebrospinal fluid and cerebrovascular endothelin concentrations during hypotension and hypertension in newborn piglets with induced sterile meningitis

The effects of sterile meningitis on endothelin-1 (ET-1) and big ET-1 concentrations during hypotension and hypertension were studied in the cerebrospinal fluid and plasma of newborn piglets. Cerebrospinal fluid was obtained via cisterna magna puncture, and blood was obtained from the sagittal sinus vein and left subclavian artery. The study group consisted of 14 newborn piglets injected with 0.5 mL heat-killed group B streptococcus (GBS) (10(9) colony forming unit (cfu) equivalents), into the right cerebral lateral ventricle; the control group consisted of 10 newborn piglets injected with sterile normal saline, in a similar fashion. Hypotension (mean arterial blood pressure (MABP) 20-59 mmHg; 1 mmHg = 133.3 Pa) and hypertension (MABP 110-140 mmHg) were induced 1.5-2 h apart in random sequence in each animal, by inflating balloon-tipped catheters placed at the aortic root and descending aorta, respectively. Cerebral blood flow (CBF) was measured using radiolabeled microspheres, 15 min before and after injection of GBS or saline (normotension), during the hypotension and hypertension episodes, and during recovery normotension, immediately prior to cerebrospinal fluid and blood sampling. ET-1 and big ET-1 concentrations (pg/mL) were measured using radioimmunoassay kits. The combined effect of induced sterile meningitis and induced hypotension resulted in a significant rise in the concentration of cerebrospinal fluid ET-1 (control, 5.1 +/- 0.1; GBS, 9.3 +/- 0.2 pg/mL; p < 0.01), cerebrospinal fluid big ET-1 (control, 0; GBS, 18.1 +/- 2.7 pg/mL; p < 0.01), and sagittal sinus (cerebrovascular) big ET-1 (control, 15.5 +/- 4.2; GBS, 47.5 +/- 9.6 pg/mL; p < 0.01). In contrast, the combined effect of induced sterile meningitis and induced hypertension resulted in a marked elevation in cerebrovascular ET-1 concentrations (control, 9.5 +/- 0.9; GBS, 28.5 +/- 6.1 pg/mL; p < 0.01), with no significant change in cerebrospinal fluid concentrations. In addition, cerebrovascular production of ET-1 increased dramatically during hypertension in the GBS group (control, 0; GBS, 161.7 +/- 13.2 pg.min-1.100 g-1; p < 0.001), and was maintained during the recovery period (133.7 +/- 10.8 pg.min-1.100 g-1). Cerebrovascular ET-1 concentrations correlated significantly with total CBF and MABP in both groups of animals (control, r = 0.49, p < 0.002; GBS, r = 0.64, p < 0.0001), but the response was of a much greater magnitude in the GBS group. There was an inverse relationship between cerebrovascular big ET-1 concentrations and total CBF (r = -0.53, p < 0.0001) and MABP (r = -0.71, p < 0.0001) in the GBS group. In the MABP range of 60-110 mmHg a positive relationship was observed between cerebrovascular ET-1 concentrations and cerebral vascular resistance, in the control group only (r = 0.59, p < 0.002). The combined insult of induced sterile meningitis and induced hypotension or hypertension may be associated with increased cerebrovascular ET-1 and (or) big ET-1 concentrations. Changes in these vasoactive agents may contribute to pressure passivity of CBF in the newborn with meningitis.