Normal angiogram after myocardial infarction in young patients:: A prospective clinical-angiographic and long-term follow-up study

This is an observational study in which we compared the clinical characteristics and the long-term course of young patients having acute myocardial infarction and angiographically normal coronary arteries and young patients showing significant coronary artery disease. In 87 patients aged ≤40 years who suffered an acute myocardial infarction, enrolled in a prospective study over a period of 6.5 years, coronary anatomy was determined by angiography within a month of admission. The risk factors, clinical data, ventricular function and the long-term outcome were compared between patients with normal angiograms (Group 1, n=12) and patients with coronary artery disease (Group 2, n=75). Patients in Group 1 had a lower number of risk factors associated with them (17% vs. 64% with >1 risk factor, P<0.005), were younger (32±5 vs. 36±4, P<0.01), lighter smokers (25% vs. 55% for ≥2 packs per day, P<0.05), had less frequent hypertension (0 vs. 25%, P<0.05), hypercholesterolemia (17% vs. 52%, P=0.02) and had a lower mean total cholesterol level (201±42 vs. 245±60 mg/100 ml, P<0.05) than patients in Group 2. They also had a more common onset of their infarction during heavy physical exertion (67% vs. 17%, P<0.001). A history of previous myocardial infarction, infarct location, global left ventricular function and regional wall motion were similar in both groups. After a mean follow-up period of 41±23 months, no patient died or had a second myocardial infarction in Group 1, and 4 patients had died in Group 2. The appearance of angina, less frequent in Group 1 than Group 2, tended to correlate with the extension of the coronary artery disease. We concluded that young patients with myocardial infarction have good prognosis irrespective of the coronary anatomy, although patients with normal coronary angiograms had less risk factors and less frequent new ischaemic events.     

Post-exercise response of the systolic blood pressure in the diagnosis of coronary artery disease: comparison of two exercise methods

We studied 81 angiographically documented coronary artery disease patients and 28 with normal coronary arteries, having paired exercise tests (the Bruce treadmill protocol and the jogging in place test) in order to investigate the value of the ratio of recovery systolic blood pressure to peak exercise systolic blood pressure (postexercise pressure ratio) compared to the classic ST depression. The postexercise pressure ratio was significantly higher in patients with coronary artery disease than in patients with normal coronary arteries for each of the 2 exercise tests (P < 0.001 − P < 0.00001). On the contrary, we obtained significantly lower sensitivities for the pathologic (> ± 2 SD of patients with normal coronary arteries) values of the post-exercise pressure ratio than for the positive electrocardiographic outcome 30% vs 58% (P < 0.00002) and 37% vs 64% (P < 0.0001) as well as lower accuracies 48% vs 63% (P < 0.03) and 52% vs 71% (P < 0.005), respectively.

Thus, we proved that the classic ST depression has much more diagnostic value than the post-exercise pressure ratio and this result is independent of the exercise methodology. Consequently this ratio is not recommended to replace the electrocardiographic exercise criteria.     

Plasma homocysteine and the extent of atherosclerosis in patients with coronary artery disease

Homocysteine is a graded risk factor for the incidence of stroke and for the degree of carotid atherosclerosis. Homocysteine is also a graded risk factor for the incidence of myocardial infarction but we do not know its precise relations to the severity of atherosclerosis in coronary patients. Seventy five symptomatic coronary patients were recruited for the study. Fifty of these patients had coronary artery disease only and were compared in a case-control manner to 50 healthy controls matched for age and sex. The 25 other coronary patients had also symptoms in another atherosclerotic territory (cerebral, peripheral or both) and were also compared to 25 matched controls. Mean plasma homocysteine level was significantly higher in coronary patients than in controls (11.7±0.7μmol l⁻¹, n=50 versus 9.9±0.5μmol l⁻¹, n=50, p<0.05). Homocysteine in patients with symptomatic atherosclerosis in two or three arterial sites was 15.7±1.5μmol l⁻¹ which differed significantly from matched controls and from patients with coronary artery disease only (p=0.01). The extent of coronary atherosclerosis evaluated by an angiographic coronary score correlated weakly to plasma homocysteine levels (r=0.25, p<0.05). The patients with both hypertension and high levels of homocysteine (>11.3μmol l⁻¹, median value) had more severe coronary atherosclerosis (coronary score of 16.3±2.3 versus 11.9±0.9, p<0.05) and more diffuse atherosclerosis (number of atherosclerotic territories of 1.5±0.2 versus 1.2±0.7, p=0.08) than the coronary patients without this association. There were no other high risk association when considering the other classical risk factors.

Thus, the highest levels of homocysteine were present in patients with coronary disease and another symptomatic localisation of atherosclerosis. A small gradient in the extent of coronary atherosclerosis was found with increasing levels of homocysteine. The presence of both hypertension and hyperhomocysteinemia was associated with more severe coronary atherosclerosis.     

Temporal relation of changes in regional coronary flow and myocardial lactate and nucleoside metabolism during pacing-induced ischemia

The temporal relation between myocardial lactate and hypoxanthine metabolism and regional changes in krypton-81m perfusion during pacing-induced ischemia was studied in 17 patients with coronary artery disease (CAD). During incremental atrial pacing, lactate production and hypoxanthine release occurred early and simultaneously, accompanied by ST-segment changes, but before angina and only few minutes after a significant (17%) reduction in krypton-81m perfusion in areas with more than 90% luminal diameter reduction. During maximal pacing heart rates, krypton-81m distribution decreased to 68 ± 7% of control in areas with more than 90% diameter reduction and to 80 ± 4% in 70 to 90% reduction (both p < 0.05 vs control). Maximal lactate production occurred 15 seconds after pacing (extraction −15 ± 7% vs 16 ± 2% during control, p < 0.05) and peak hypoxanthine release 1 minute after pacing (Δ arteriovenous −2.64 ± 0.8 μM vs 0.08 ± 0.21 μM during control, p < 0.05). Krypton-81m perfusion decreased in 20 of the 21 CAD areas. Angina, ST-segment changes, hemodynamic alterations and lactate production occurred in 15, 14, 9 and 15 patients, respectively. In contrast, hypoxanthine release was found in all cases. After pacing, lactate production and all general indexes of ischemia persisted for only 2 to 3 minutes. In contrast, krypton-81m perfusion was still significantly reduced 5 minutes after pacing and was only accompanied by hypoxanthine release (Δ arteriovenous −1.41 ± 0.6 μM, p < 0.05 vs control). Therefore, although lactate production and hypoxanthine release occur early and simultaneously during pacing-induced ischemia, closely following coronary flow changes in high-stenotic areas, hypoxanthine appears to be more sensitive and consistent as indicator of ischemia. Persistant reductions in krypton-81m perfusion and hypoxanthine release strongly suggest prolonged ischemia after cessation of pacing.     

Microsomal triglyceride transfer protein: does insulin resistance play a role in the regulation of chylomicron assembly?

We have previously demonstrated that diabetes is associated with an increase in intestinal microsomal triglyceride transfer protein (MTP) mRNA in both the rat and rabbit models. The present study was designed to investigate the relationship between MTP expression and chylomicron assembly in an insulin resistant non-diabetic animal model. Ten insulin resistant Zucker obese fa/fa rats and ten lean fa/− rats were examined at 8–10 weeks of age. The lymph duct was cannulated and lymph collected for 4 h. Lymph chylomicrons were isolated by ultracentrifugation and their composition determined. RNA was extracted from intestinal mucosa and from the liver. MTP mRNA was measured using the RNase protection assay. Blood sugar in the fatty rats was significantly higher (6.3±1.2 vs. 5.4±0.4 P<0.05) and plasma insulin was almost six times that of the lean rats (P<0.001). Plasma cholesterol and phospholipid but not triglyceride were significantly increased in the obese animals (P<0.01). Obese animals secreted significantly more lymph chylomicron apo B48 (0.05±0.02 vs. 0.02±0.01mg/h P<0.005), triglyceride (9.7±5.3 vs. 3.8±1.9 mg/h P<0.005) and phospholipid (1.5±0.7 vs. 0.4±0.3 mg/h P<0.001). The only difference in the chylomicron particle composition between the two groups was a significant increase in phospholipid (P<0.01). Intestinal MTP mRNA expression was significantly higher in the fatty compared to the lean rats (22.1±9.5 vs. 7.8±5.6 amol MTP mRNA/μg total RNA P<0.001) as was hepatic MTP mRNA expression (6.9±3.5 vs. 3.4±1.5 amol MTP mRNA/μg total RNA, P<0.01). Thus in this animal model of insulin resistance, increased MTP, which was associated with increased chylomicron particle number, may play a crucial role in the development of atherosclerosis.     

Spontaneous echo contrast in the descending aorta in patients without aortic dissection: associated clinical and echocardiographic characteristics

The objective of the study was to evaluate the frequency, clinical and echocardiographic correlates of spontaneous echo contrast in the descending aorta in the absence of dissection. Prevalence of spontaneous echo contrast in the descending aorta in the absence of dissection, and its clinical and echocardiographic correlates were investigated in 1199 consecutive patients who underwent transesophageal echocardiography. Spontaneous echo contrast in the descending aorta was detected in 54 (4.5%) patients. Patients with spontaneous echo contrast in the descending aorta had an older age (60.6±8 vs. 40.6±14.2 years, P=0.0001), an increased prevalence of male gender (66.7 vs. 43.9%, P=0.001), an increased diameter of ascending aorta (4.2±1.0 vs. 3.3±1.1 cm, P=0.0001), an increased diameter of descending aorta (3.1±0.9 vs. 2.1±0.4 cm, P=0.0001), a higher prevalence of aortic wall calcification (9.3 vs. 0.5%, P=0.00001), complex plaque in the descending aorta (13 vs. 0.7%, P=0.0001), left ventricular dysfunction (7.4 vs. 2.1%, P<0.05), a lower incidence of severe aortic regurgitation (0 vs. 3.5%, P<0.05), a lower peak flow velocity in the descending aorta (28±9 vs. 51±21 cm/s, P<0.00001), and a lower maximal shear rate in the descending aorta (51±29 vs. 105±47 s⁻¹, P<0.00001) compared with patients without spontaneous echo contrast in the descending aorta. However, prevalence of atrial fibrillation, mitral valve disease, intracardiac spontaneous echo contrast and/or thrombus and embolic event were not different between patients with and without spontaneous echo contrast in the descending aorta (P>0.05). Shear rate, diameter of the descending aorta, aortic wall calcification, complex plaque in the descending aorta, absence of severe aortic regurgitation and male gender were independent variables of spontaneous echo contrast in the descending aorta. Spontaneous echo contrast in the descending aorta is a local and flow-dependent phenomenon related to aortic dilation, atherosclerosis, and decreased shear rates in the descending aorta. However, in this study, spontaneous echo contrast in the descending aorta was not found to be associated with embolic events.     

Reduced platelet serotonin content and release in familial hypercholesterolaemia

Plasma and platelet serotonin (5-HT) concentrations, and resting and collagen-induced 5-HT release in platelet-rich plasma were studied in normal and familial hypercholesterolaemic (FH) subjects. Platelet 5-HT concentrations were significantly reduced (−37%, P<0.01) in FH patients whilst mean plasma concentrations, although increased, were not significantly different from those in normal subjects. Platelet 5-HT correlated negatively with plasma cholesterol when the data for normal subjects and FH patients were combined (r=−0.48, P=0.005). It also correlated negatively with low-density lipoprotein (LDL) (FH data, r=−0.59, P=0.03; normal and FH data, r=−0.49, P=0.004) but positively with high-density lipoprotein (HDL) (FH, r=0.79, P=0.001; normal and FH, r=0.37, P=0.03). Collagen (5–160 μg/ml) stimulated platelet 5-HT release occurred in a concentration-dependent manner. In FH patients stimulated 5-HT release was reduced (10 μg/ml collagen, −40%, P<0.05) and accompanied by increased collagen EC₅₀ values (P<0.02). Resting 5-HT release was increased substantially in FH patients but not significantly. Our data provide evidence for a relationship between circulating cholesterol and platelet serotonergic mechanisms. It is proposed that abnormalities relating to platelet-plasma 5-HT dynamics, perhaps due to enhanced platelet activity or decreased platelet uptake, may contribute to the cardiovascular complications in FH.     

Activation of CD14 on circulating monocytes in patients with acute coronary syndrome

Background: Increasing evidence supports the involvement of inflammation in acute phase of coronary artery diseases. Methods: We analyzed the status of activation of inflammatory cells in 38 patients with acute coronary syndrome, 14 stable angina patients, and 19 control subjects by flow-cytometry. Expression levels of CD14 and the percentage of HLA-DR⁺ T-lymphocytes were used as markers of monocyte and T-lymphocytes activation, respectively. Results: The expression of CD14 on monocytes in acute coronary syndrome patients (mean fluorescence intensity±S.D.=158.1±77.1) was increased significantly in comparison to control subjects (57.1±8.0) and the stable angina group (63.6±22.0) (P<0.0001 for both). A significantly higher percentage of HLA-DR positive T-lymphocytes (20.4±9.0 vs. 12.7±3.7%, P<0.01) was observed in acute coronary syndrome patients in comparison to control subjects. Incubation of whole blood cells with bacterial lipopolysaccharide resulted in a 2.4-fold higher secretion of tumor necrosis factor- in acute coronary syndrome patients than in control subjects (P<0.05). When these markers of activation were measured in acute coronary syndrome patients 6 weeks after medical treatment, a significant reduction both in monocytic CD14 expression and percentage of HLA-DR positive T-lymphocytes (P<0.05 for both) was observed. Discussion: We observed markedly increased levels of monocytic CD14 expression in ACS patients, which appear to indicate the activated status of monocytes and hyper-responsiveness to external stimuli. The CD14 expression levels decreased as the patients were treated, indicating that the expression of CD14 accurately represents the activation status of monocytes during the acute phase of coronary artery diseases.     

Inhibition of lipoprotein lipase induced cholesterol ester accumulation in human hepatoma HepG2 cells

It has been suggested previously that lipoprotein lipase may act as a ligand to enhance binding and uptake of lipoprotein particles. In the present study we have examined the capacity of bovine milk lipoprotein lipase to induce intracellular accumulation of triglyceride and cholesterol ester by VLDL (S_f 60–400) isolated from Type IV hypertriglyceridemic subject (HTg-VLDL) in HepG2 cells, independent of its lipolytic activity. We have also attempted to elucidate the cellular receptor mechanisms responsible for these effects. HTg-VLDL-mediated increases in intracellular triglyceride and cholesterol ester were dependent on the presence of an active lipase. Bovine milk lipoprotein lipase (LPL) increases triglyceride mass by 301% ± 28% (P < 0.0005) and cholesterol ester mass by 176% ± 12% (P < 0.0005). These HTg-VLDL-mediated increases in intracellular triglyceride and cholesterol ester did not occur when heat-inactivated lipase was used. Rhizopus lipase could replace LPL and cause equivalent increases in intracellular triglyceride and cholesterol ester (472% ± 61% (P < 0.005) and 202% ± 25% (P < 0.025) respectively vs. control). HTg-VLDL treated with LPL and reisolated also caused equivalent increases (274% ± 18% (P < 0.01) and 177% ± 12% (P < 0.005) for triglyceride and cholesterol ester). LDL also caused increases in intracellular cholesterol ester (189% ± 20% (P < 0.005)), although three times more LDL cholesterol had to be added to achieve the same effect. These LDL-induced increases were effectively blocked by monoclonal antibodies directed against the B,E receptor binding domains of apo B (−97% ± 13% (P < 0.0005) with anti-apo B 5E11 and − 68% ± 13% (P < 0.05) for anti-apo B B1B3) or by anti-B,E receptor antibodies (− 77% ± 7% (P < 0.01) antibody C7). These same antibodies had little effect on the HTg-VLDL + LPL-induced increases in cholesterol ester (+21%, + 15% and − 22% for 5E11, B1B3 and C7, respectively). Monoclonal anti-apo E antibodies also had no effect on LDL-mediated increases in intracellular cholesterol ester, but had a small and significant effect on VLDL-mediated increases in cholesterol ester. However, heparin, which interferes with cell surface proteoglycan interaction, was very effective at blocking HTg-VLDL-mediated increases in cholesterol ester in the presence of LPL (− 86% ± 8% P < 0.0005). Heparin was also effective in the presence of Rhizopus lipase (−79%) or lipolyzed re-isolated HTg-VLDL (−95%). These results suggest that lipoprotein lipase may enhance the uptake process beyond its role in lipolytic remodelling but does not appear to be an absolute requirement. In contrast, heparin had no effect on LDL-mediated cholesterol ester accumulation. Lactoferrin, which inhibits interaction with the low density lipoprotein receptor-related protein (LRP), was also very effective at inhibiting HTg-VLDL increases in intracellular cholesterol ester (− 95% ± 6%, P < 0.01). However, there was no effect of either heparin or lactoferrin on HTg-VLDL-mediated triglyceride accumulation. Thus cell surface heparin sulphate may facilitate intracellular lipid acquisition by providing a stabilizing bridge with the lipoproteins and enhance uptake through receptor-mediated processes such as LRP.     

Differential effects of antihypertensive drug therapy on arterial compliance

Although vascular compliance, ΔV/ΔP, is abnormal in essential hypertension and can be improved by antihypertensive drug therapy, it is not clear whether drug-induced changes in compliance are attributable solely to lower achieved blood pressure (BP), and thus equally likely with different drugs possessing similar antihypertensive efficacy. Therefore, we used computerized arterial pulse waveform analysis (CAPWA) to measure capacitive (C1) and oscillatory (C2) components of arterial compliance in essential hypertensive subjects (n = 39) before, and 1 and 3 months after achieving normotensive BP values with administration of either dihydropyridine calcium channel antagonists (CaBl, n = 11), converting enzyme inhibitors (CEI, n = 9), angiotensin receptor blockers (ARB, n = 9), or β-blockers (BBl, n = 10).

Despite equivalent effects on BP (CaBl: −19 ± 4/−15 ± 2 mm Hg; CEI: −12 ± 3/−13 ± 2 mm Hg; ARB: −10 ± 3/−12 ± 2 mm Hg; and BBl: −14 ± 3/−12 ± 2 mm Hg; P < .005 for each drug v pretreatment), CaBl, CEI, and ARB significantly increased arterial compliance (CaBl: %ΔC1 = 30.0 ± 5.8, %Δ C2 = 43.7 ± 23.3; CEI: %ΔC1 = 32.7 ± 5.4, %ΔC2 = 26.7 ± 7.1; ARB: %ΔC1 = 36.3 ± 11.8, %ΔC2 = 43.6 ± 23.1; P < .01 for CaBl, CEI, and ARB v pretreatment), but BBl did not (%ΔC1 = −3.9 ± 7.6, %ΔC2 = −7.0 ± 11.5, P = not significant v pretreatment, SIG = 0.01 v other drugs). We conclude that for an equivalent effect on BP, arterial compliance improves after therapy with some, but not all antihypertensive drugs. We hypothesize that a greater clinical benefit may result from the preferential use of drugs that concomitantly improve arterial compliance.     

Plasma osteopontin levels are associated with the presence and extent of coronary artery disease

Recently, osteopontin (OPN) mRNA was reported to be highly expressed in atherosclerotic plaques, most strikingly in calcified plaques. We examined if plasma OPN levels are associated with coronary stenosis and calcification in patients with coronary artery disease (CAD). We measured plasma OPN levels in 178 patients undergoing coronary angiography. Compared with 71 patients without CAD, 107 with CAD had higher OPN levels (616±308 ng/ml versus 443±237 ng/ml, P<0.001). A stepwise increase in OPN levels was found depending on the number of >50% stenotic coronary vessels: 540±293 ng/ml in 1-vessel, 615±230 ng/ml in 2-vessel, and 758±416 ng/ml in 3-vessel disease. OPN levels also correlated with the numbers of >50% and >25% stenotic segments (r=0.35 and 0.43, respectively, P<0.001). In multivariate analysis, OPN levels were significantly associated with CAD (odds ratio=1.21, 95% CI=1.05–1.39 for a 100 ng/ml increase) independent of traditional risk factors. Coronary calcification was found in 86 patients. OPN levels were higher in patients with calcification than in those without calcification (608±328 ng/ml versus 490±246 ng/ml, P<0.01) and correlated with the number of calcified segment (r=0.26, P<0.001). However, OPN levels were not independently associated with coronary calcification. Thus, plasma OPN levels were found to be associated with the presence and extent of CAD.     

Segmental blood flow and rheological determinants in diabetic patients with peripheral occlusive arterial disease

Vascular abnormalities are more prevalent in the lower extremities in diabetic patients and may cause diminished perfusion to surrounding tissues. We sought to identify blood flow abnormalities in the leg of diabetic patients with peripheral occlusive arterial disease (POAD) and to determine whether these were associated with abnormalities in rheological determinants, namely, plasma fibrinogen concentration (PFC), relative plasma viscosity (RPV), hematocrit (Hct), and whole blood viscosity (WBV). Seventeen diabetic patients with POAD were compared with 40 diabetic patients without POAD and 19 nondiabetic control subjects. Blood flow was measured by venous occlusion plethysmography, RPV was measured by capillary viscometry, WBV was measured by a Wells–Brooksfield viscometer [at high (230 s⁻¹) and low (23 s⁻¹) shear rates], and PFC was measured by the clot–weight method of Ingram [Ingram, G. I. C. (1961). A suggested schedule for the rapid investigation of acute haemostatic failure. Journal of Clinical Pathology, 14, 356–360]. Ankle blood flow (Q_ak) was significantly lower in diabetic patients with POAD than in diabetic patients without POAD (P<.05). PFC was higher and Hct was lower in diabetic patients with POAD than in diabetic patients without POAD (P<.05). RPV was 1.97±0.15 versus 1.92±0.15 in diabetic patients with POAD and diabetic patients without POAD, respectively (P>.05). There was no significant difference in WBV at low or high shear rates between the groups studied. There was a correlation between WBV at low shear rate and arterial flow in the calf (Q_c) (r=.94) and great toe (r=.95) in diabetic patients with POAD, and between Q_c and WBV at high (r=−.465) and low (r=−.472) shear rates in diabetic patients without POAD (P<.05). We conclude that vasodilatation occurring in diabetic patients without POAD is severely restricted or absent in diabetic patients with POAD. Increased plasma fibrinogen and plasma viscosity may contribute to this phenomenon.     

Fluvastatin attenuates nitrate tolerance in patients with ischemic heart disease complicating hypercholesterolemia

Background: Long-term administration of nitrates results in the development of tolerance. Nitrate tolerance is considered to occur in association with oxidative stress, although its underlying mechanisms are multi-factorial. Fluvastatin, a newly developed statin, is considered to have not only a cholesterol-lowering effect but also anti-oxidative properties. Methods: In this study, the effect of fluvastatin on nitrate tolerance was investigated in 12 dyslipidemic patients (nine men and three women, aged 63.5±6.7 years), who were complicated with ischemic heart disease and had received organic nitrates for a long period. Results: Four months after fluvastatin therapy, symptoms of angina were significantly reduced. Consumption of sublingual nitrates over 2 weeks significantly decreased (14.4±11.2 to 2.3±2.5 tablets, P<0.01). In exercise stress testing, exercise duration was significantly prolonged (275±73 to 360±86 s, P<0.01) and the blood pressure-heart rate products significantly increased (16 368±2246 to 18 381±1772, P<0.01). Both the percent change in forearm blood flow with reactive hyperemia (232±83 to 282±104%, P<0.05) and that after sublingual nitroglycerine (2.5±4.7 to 5.8±4.7%, P<0.05) were increased. Although the levels of total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol were unchanged, the serum anti-Ox-LDL titer (16.7±6.3 to 13.4±5.4 AcU/ml, P<0.05) and 8-OHdG level (1.11±0.34 to 0.73±0.34 ng/ml, P<0.05) decreased. Conclusions: Fluvastatin attenuated nitrate tolerance in dyslipidemic patients complicated with ischemic heart disease who had been receiving organic nitrates over long period. The anti-oxidative effect of fluvastatin may attenuate nitrate tolerance.     

Circulating erythropoietin in microalbuminuric type 2 diabetic patients with normal renal function: a pilot study

To verify the hypothesis of an early impairment of erythropoietin (Epo) production and to assess the adequacy of its circulating levels in diabetic nephropathy, we investigated Epo values in 18 microalbuminuric type 2 diabetic patients with normal renal function (7 anaemic and 11 nonanaemic), 24 subjects with uncomplicated iron-deficiency anaemia, and 15 healthy controls comparable for sex and age. Mean±S.D. plasma Epo level was 56.4±12.7 mU/mL in iron-deficient patients and 9.3±2.6 mU/mL in controls. In diabetic groups, mean±S.D. Epo level was 11.38±3.65 mU/mL in nonanaemic and 49.12±6.44 mU/mL in anaemic subjects. No significant difference (P>.05) in Epo values was found between controls and nonanaemic diabetic patients. Anaemic diabetics and iron-deficient subjects had significantly higher values than the nonanaemic groups (P>.001). An inverse significant relation between Epo levels and Hb concentration resulted in both anaemic diabetics (r=−.44, P>.05) and iron-deficient patients (r=−.61, P=.001). Analysis of covariance (P>.05) and comparison of the two regression lines (t=0.4, df=29, P>.05) did not show any significant difference between diabetic patients with anaemia and iron-deficient patients. These results suggest that normochromic anaemia observed in microalbuminuric diabetic patients with normal renal function is not due to Epo deficiency, and circulating levels of this hormone are suitably increased with regard to Hb concentration.     

Effects of sympathetic nerves on collateral vessels in the limb of atherosclerotic primates

This study was performed to examine effects of sympathetic nerves on collateral vessels in the limb. We studied normal (N) and atherosclerotic (AS) cynomolgus monkeys that were fed atherogenic diet for 21 months. A common iliac artery was ligated 13 months before hemodynamic measurements. Using histofluorescence microscopy, a plexus of noradrenergic nerves was identified in the adventitia of collateral vessels. We measured blood flow to the limb with microspheres, and the pressure gradient from aorta to the iliac artery beyond the occlusion. The lumbar sympathetic chain was stimulated electrically at 3 Hz (SNS-3) and 15 Hz (SNS-15). In normal monkeys, conductance of collateral vessels (in ml/min per 100 g per 100 mm Hg) was 19 ± 3.6 (mean ± SE) during control, 14 ± 1.6 during SNS-3, and 9.8 ± 0.9 during SNS-15 (P < 0.05 vs control). In AS monkeys, collateral conductance was 12 ± 2.9 during control, 7.5 ± 1.7 during SNS-3 and 3.9 ± 1.8 during SNS-15 (P < 0.05). In summary, collateral vessels in the limb are innervated and sympathetic stimulation produces pronounced constriction of collateral vessels in both normal and atherosclerotic monkeys. Thus, the effectiveness of collateral vessels in maintaining blood flow to the limb may be compromised by increased activity of sympathetic nerves.     

Ovariectomy Aggravated Sodium Induced Hypertension Associated With Altered Platelet Intracellular Ca in Dahl Rats

Our purpose was to determine the effect of ovariectomy on intracellular Ca²⁺ mobilization and platelet aggregation in sodium induced hypertension. At the age of 12 weeks ovariectomy or sham operation was performed in female Dahl-Iwai salt sensitive rats on a 0.3% NaCl diet. Four weeks later we assessed the effects of ovariectomy and an 8% NaCl diet on agonist induced intracellular Ca²⁺ mobilization in fura-2 loaded platelets and platelet aggregation. Ovariectomy enhanced the increase of systolic blood pressure and heart to body weight ratio on an 8% NaCl diet. However, thrombin evoked intracellular Ca²⁺ was not correlated with systolic blood pressure (r = −0.338, P = .17), and was lowered by sodium loading and ovariectomy (360 ± 23 to 285 ± 9, 296 ± 10 nmol/L, P < .05). Furthermore, the ionomycin induced intracellular calcium fraction in the absence of external Ca²⁺ that reflected internal Ca²⁺ discharge capacity was reduced in ovariectomized rats compared with sham operated rats on an 8% NaCl diet (648 ± 15 v 768 ± 35 nmol/L, P < .05). The internal Ca²⁺ discharge capacity was inversely correlated with systolic blood pressure (r = −0.506, P = .03). In addition to the decreased internal Ca²⁺ discharge capacity, intracellular Ca²⁺-independent platelet aggregation by phorbol 12-myristate 13-acetate, a protein kinase C activator, was significantly enhanced in hypertensive rats. We concluded that ovariectomy enhanced sodium induced hypertension associated with the decreased internal Ca²⁺ discharge capacity and increased platelet aggregation in Dahl-Iwai salt-sensitive rats.     

Comparison of Collateral Vascular Responses in the Donor and Recipient Coronary Artery During Transient Coronary Occlusion Assessed by Intracoronary Blood Flow Velocity Analysis in Patients

Objectives. This study was designed to evaluate the hemodynamic variables of the collateral circulation during acute coronary occlusion.

Background. There is limited information on the physiology of the collateral circulation in coronary artery disease.

Methods. Angiography of the contralateral donor artery was performed before and during balloon coronary occlusion in 57 patients with one-vessel disease. Recruitable collateral flow was assessed during coronary occlusion by blood flow analysis of the contralateral donor artery (n = 19) or the ipsilateral recipient artery (n = 15), or both (n = 23), using a Doppler catheter or guide wire. Ischemia was evaluated by the ST segment shift (≥0.1 mV) on a 12-lead electrocardiogram at 1 min of coronary occlusion.

Results. The presence (n = 39), compared with the absence (n = 18), of recruitable collateral vessels was associated with an increase of blood flow velocity in the donor artery (20 ± 19% vs. 4.8 ± 5.9% [mean ± SD], p = 0.003) and the recipient artery (velocity integral 7.2 ± 5.5 vs. 2.8 ± 2.2 cm, p = 0.02) related to a reduced relative collateral vascular resistance (9.2 ± 10 vs. 20 ± 11, p = 0.003). Collateral flow in the donor artery yielded a similar predictive value for recruitability of collateral vessels as collateral flow determined in the recipient artery or the coronary wedge/aortic pressure ratio (areas under the receiver operating characteristics curves 0.76 ± 0.07, 0.78 ± 0.08, 0.77 ± 0.07, respectively, p = NS). Collateral flow in the recipient artery was a better predictor for ischemia than collateral flow in the donor artery or angiographic grading of collateral vessels (areas 0.90 ± 0.05, 0.64 ± 0.10, 0.73 ± 0.07, respectively, p < 0.05).

Conclusions. Coronary blood flow velocity analysis of the donor and recipient coronary arteries can characterize the dynamics of the collateral circulation during acute coronary occlusion. The protective effect of recruitable collateral vessels relates to an increase of flow in the donor and recipient coronary arteries due to a reduced collateral vascular resistance. This study underscores the importance of physiologic variables for the evaluation of the function of recruitable collateral vessels.

(J Am Coll Cardiol 1997;29:1528–35)     

Functional Myocardial Perfusion Abnormality Induced by Left Ventricular Asynchronous Contraction: Experimental Study Using Myocardial Contrast Echocardiography

Objectives. The aim of this study was to clarify how myocardial perfusion is impaired by asynchronous contraction.

Background. False septal hypoperfusion is noted in some patients with left bundle branch block.

Methods. Eight dogs were examined with epicardial pacing at the left ventricular posterior wall, the right ventricular anterior wall and, as a control, the right atrial appendage. The pacing rate was 80, 110 and 150 beats/min (bpm). Myocardial perfusion was assessed by contrast echocardiography.

Results. Left ventricular pacing at 80 and 110 bpm did not change systolic wall thickening or contrast intensity at the pacing site, although an early excitation notch was noted at the pacing site. However, at 150 bpm, systolic thickening was impaired (23.3 ± 4.2% vs. 37.0 ± 2.6% during atrial pacing, p < 0.05), and the peak intensity ratio of the pacing site to the ventricular septum was significantly decreased (24.1 ± 5.7% vs. 37.0 ± 2.8% at a pacing rate of 80 bpm, p < 0.01). The peak intensity ratio correlated with systolic wall thickening at the pacing site (y = 0.413 × −0.028, r = 0.81, p < 0.0001). However, right ventricular pacing did not change either systolic thickening or the peak intensity ratio at any pacing rate, although an early excitation notch was noted on the ventricular septum.

Conclusions. Wall motion abnormalities after early excitation vary depending on the pacing mode. When tachycardia induces regional wall motion abnormalities, the ventricular wall of the pacing site is functionally hypoperfused.

(J Am Coll Cardiol 1997;29:1632–8)     

The development of the adrenal gland zona glomerulosa in the rat. A morphological, immunohistochemical and biochemical study

We have studied the development of the adrenal gland in the rat comprising the ages ranging from 0 to 90 days after birth. The weight of the animals and that of the adrenal glands demonstrated a linear growth with time until 75 days, both in males and females. The area of the zona glomerulosa (ZG) increased in size from birth until ≈40 days of age. After that, growth had a much smaller slope (females, r=0.84, P<0.001; males, r=0.81, P<0.001). Aldosterone secretion had a marked increase until 20 days of age and thereafter demonstrated a tendency for a decrease (females, r=−0.19, P<0.02; males r=−0.26, P<0.001). Plasma renin activity followed a trend parallel to that of aldosterone. The steroid precursor 18-OH-deoxycorticosterone (18-OH-DOC) demonstrated a different course as it increased progressively with age especially in the females (females, r=0.57, P<0.001; males, r=0.40, P<0.001). The expression of the enzyme 3-β-hydroxysteroid dehydrogenase (3-β-HSD) was also studied by immunohistochemistry and it was shown to be very low at birth and starting to increase by 10 days of age. After 30/40 days of age the amount of this enzyme existing in the ZG was comparable with that of the outer zona fasciculata (ZF). We conclude that the development of the ZG in the rat has particularities that make it different from that of the rest of the cortex.     

Association between hematological parameters and metabolic syndrome components in a Chinese population

Insulin resistance, an essential core contributing to the metabolic syndrome (MS), has been demonstrated in some studies to be associated with white blood cell (WBC) or red blood cell (RBC) counts. The present study was undertaken to assess systemically the relationship between WBC or RBC counts and various clinical features of MS in a large Chinese population at Taiwan. A total of 4938 subjects (2891 men and 2047 women with a mean age of 50.1±12.6 years), who had attended health examination at this hospital were enrolled. The Adult Treatment Panel III (ATP III) definition of MS components was adopted in this study with the exception of the definition of obesity. This was defined as body mass index (BMI) greater than 27 kg/m². Overall, 14% had high serum total triglyceride (TG), 8% had low high-density lipoprotein (HDL) cholesterol, and 18% were obese. WBC counts showed a statistically significant (P<.001) correlation with TG (r=.265), HDL(r=−.187), fasting glucose (r=.084), and BMI (r=.172) but not with blood pressure levels. In addition, RBC counts correlated significantly (P<.001) with TG (r=.250), HDL(r=−.269), fasting glucose (r=.098), and BMI (r=.228). WBC and RBC counts in subjects grouped according to the presence of 0, 1, 2, and ≥ 3 features of MS were 6268±1633, 6555±1782, 6995±1880, and 7185±1696 cells/mm³, and 4.63±0.56×10⁶, 4.73±0.54×10⁶, 4.84±0.60×10⁶, and 4.91±0.55×10⁶ cells/mm³, respectively (P for trend <.001). Subjects in the highest quartile of WBC or RBC counts demonstrated a three- or twofold increase, respectively, in the odds ratio for MS with 3 or more metabolic features compared to subjects in the lowest quartile of WBC or RBC counts. Increased WBC and RBC counts, albeit normal, were associated with a variety of MS features in a Taiwan Chinese population, suggesting that hematological parameters could potentially be used as indicators of this syndrome.