PubMed Health⌕ Search

Biomedical subjects

K Chatterjee

Publications and source records attributed to K Chatterjee.

At least 73 records · Page 4Linked to original sources
PubMed1995

Mechanisms of estrogen-induced vasodilation: in vivo studies in canine coronary conductance and resistance arteries.

OBJECTIVES: We sought to examine the immediate vasodilator effect of intracoronary estrogen on epicardial and resistance coronary arteries in 19 dogs. BACKGROUND: Although estrogen reportedly dilates coronary arteries in vitro, the site and mechanisms of its action have not been fully defined in vivo. METHODS: Epicardial coronary artery dimensions and coronary flow velocity were assessed using simultaneous intracoronary two-dimensional and Doppler ultrasound. RESULTS: Estrogen (0.1 and 1 mumol/liter) induced a significant increase in coronary cross-sectional area, flow velocity and volumetric blood flow. Estrogen-induced vasodilation was not influenced either by pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME) (100 mumol/liter intracoronary), indomethacin (5 mg/kg body weight intravenously), propranolol (0.75 mg/kg intravenously) or the classic estrogen receptor antagonist ICI 182,780 (10 mumol/liter). Balloon denudation of the endothelium did not attenuate estrogen-induced epicardial vasodilation. Pretreatment with glibenclamide (10 mumol/liter) attenuated estrogen-induced vasodilation only in epicardial arteries, as did verapamil (0.1 mumol/liter). Estrogen had no effect on a phenylephrine dose-response curve in either epicardial coronary arteries or the microcirculation. CONCLUSIONS: Acute estrogen-induced dilation in canine coronary arteries is endothelium independent and is not mediated by the classic intracellular estrogen receptor but through non-genomic mechanisms, presumably at the membrane level, which in epicardial arteries may include effects on adenosine triphosphate-sensitive potassium or calcium channels, or both.

Analysis of Variance↗
PubMed1994

Effect of orthotopic cardiac transplantation on peripheral vascular function in congestive heart failure: influence of cyclosporine therapy.

The objective of this study was to examine peripheral vascular function before and after cardiac transplantation and to assess the effect of immunosuppressive therapy on peripheral vascular reactivity. Peripheral vascular function abnormalities present in congestive heart failure may be reversed with cardiac transplantation, but immunosuppressive therapy may alter these changes in the peripheral vasculature. Venous occlusion plethysmography was used to study peripheral vascular function in nine patients with severe congestive heart failure who underwent cardiac transplantation. Forearm blood flow and forearm vascular resistance were measured in patients with congestive heart failure in response to cold stimulation, maximal hyperemia, and hand grip exercise (1) before transplantation; (2) 24 to 36 hours posttransplantation before the commencement of cyclosporine; (3) 6 to 8 days posttransplantation in the presence of therapeutic cyclosporine levels; and (4) 6 weeks posttransplantation. Venous capacitance was also measured. After cardiac transplantation, mean arterial pressure increased and remained elevated. Forearm blood flow initially increased after transplantation but subsequently decreased with cyclosporine. Cold-induced reflex sympathetic activation decreased immediately after transplantation but was significantly enhanced with cyclosporine. The maximal vasodilatory response following ischemic cuff occlusion and with 5 minutes of isometric hand grip exercise increased significantly after transplantation and remained improved at 6 weeks. Thus after cardiac transplantation, peripheral vasodilator function improves and is not altered by cyclosporine. However, with cyclosporine therapy resting forearm vascular resistance increases and reflex sympathetic vasoconstriction is enhanced, suggesting that cyclosporine may potentiate adrenergic-mediated peripheral vasoconstriction and thus may contribute to posttransplant hypertension.

Analysis of Variance↗
PubMed1994

Measurement of volumetric coronary blood flow by simultaneous intravascular two-dimensional and Doppler ultrasound: validation in an animal model.

We examined the accuracy and feasibility of using simultaneous intracoronary Doppler and two-dimensional (2D) ultrasound imaging in the measurement of volumetric coronary blood flow (CBF). A femoral artery-to-circumflex coronary artery shunt was created in four dogs with tubing that incorporated an in-line transit-time ultrasound (TTU) flow probe. A 2D ultrasound catheter was introduced over a 0.014-inch Doppler guide wire into the circumflex artery with the guide wire tip positioned 2 cm beyond the imaging catheter tip. Cross-sectional area (CSA) and average peak velocity (APV) were recorded. CBF was determined from the previously validated relation CBF = CSA x 0.5 APV and the adjusted measurement formula CBF = CSA x 0.47 APV. Within the 119 measurements made, TTU CBF varied from 31 to 385 ml/min. An excellent correlation was found between 2D/Doppler-derived and TTU CBF with both constants; measurement agreement was improved and bias minimal with the 0.47 constant (slope = 0.9997; r = 0.99; p < 0.0001; SEE = -6.7 +/- 8.6). We conclude that simultaneous 2D and Doppler ultrasound yields accurate estimates of volumetric CBF.

Animals↗
PubMed1994

Differential contribution of nitric oxide to regulation of vascular tone in coronary conductance and resistance arteries: intravascular ultrasound studies.

We examined the role of nitric oxide in the maintenance of coronary vascular tone in 15 dogs. A 0.014 inch Doppler wire was introduced into the midsegment of the circumflex coronary artery and a 4.3F, 30 MHz two-dimensional ultrasound imaging catheter was introduced over the Doppler wire. Acetylcholine caused a dose-dependent vasodilation in both epicardial and resistance coronary arteries. However, N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthetase caused a dose-dependent vasoconstriction mainly in the epicardial coronary arteries, partially reversed by L-arginine. The vasodilator response to acetylcholine was inhibited by L-NAME only in the epicardial circulation. Thus using combined intracoronary two-dimensional and Doppler ultrasound, we have demonstrated both basal and acetylcholine-induced release of nitric oxide in epicardial coronary arteries. The failure of L-NAME to decrease basal and acetylcholine-induced increases in flow velocity suggests that endothelium-dependent relaxation in coronary resistance vessels may not be mediated by nitric oxide alone.

Acetylcholine↗
PubMed1994

Improved hemodynamic function and mechanical efficiency in congestive heart failure with sodium dichloroacetate.

OBJECTIVES: The purpose of this study was to determine whether sodium dichloroacetate improves hemodynamic performance and mechanical efficiency in congestive heart failure. BACKGROUND: Congestive heart failure is associated with impaired hemodynamic performance and reduced mechanical efficiency. Dichloroacetate stimulates pyruvate dehydrogenase activity by inhibition of pyruvate dehydrogenase kinase, which results in inhibition of free fatty acid metabolism and stimulation of high respiratory quotient glucose and lactate consumption by the heart. Facilitation of glucose and lactate consumption with dichloroacetate should improve mechanical efficiency of the failing ventricle. METHODS: Ten patients with New York Heart Association functional class III to IV congestive heart failure were studied. Dichloroacetate (50 mg/kg body weight) was administered intravenously for 30 min, with measurements of hemodynamic variables, coronary sinus blood flow and blood gas, glucose and lactate levels for 2 h. The same patients were also given dobutamine (5 to 12.5 micrograms/kg per min) for comparison. RESULTS: Therapeutic levels of dichloroacetate were achieved (100 to 160 micrograms/liter of plasma). Myocardial consumption of lactate was stimulated from 29% to 37.4%. Forward stroke volumes increased (+5.3 ml/beat, p < 0.02), as did left ventricular stroke work (+1.8 g-m/m2 per beat, p < 0.02) and left ventricular minute work (from 1.38 to 1.55 kg-m/m2 per min, p < 0.01). Myocardial oxygen consumption decreased (from 19.3 to 16.5 ml/min, p = 0.06) as left ventricular minute work increased. Left ventricular mechanical efficiency thus improved from 15.2% to 20.6% (p = 0.03). Dobutamine administration resulted in the opposite trend with respect to myocardial lactate extraction (from 34% to 15.3%, p < 0.02). Stroke volume increased (+7.4 ml/beat, p = NS vs. dichloroacetate), as did left ventricular minute work (from 1.29 to 1.59 g-m/m2 per min, p < 0.01 vs. dichloroacetate) and myocardial oxygen consumption (from 18.6 to 21.0 ml/min, p = 0.06 vs. dichloroacetate). Left ventricular mechanical efficiency did not change with dobutamine administration (from 16.4% to 15.8%, p = NS). CONCLUSIONS: Dichloroacetate administration stimulates myocardial lactate consumption and improves left ventricular mechanical efficiency. Forward stroke volume and left ventricular minute work increase significantly, with a simultaneous reduction in myocardial oxygen consumption. Dobutamine administration results in similar hemodynamic improvements but with no change in left ventricular mechanical efficiency and with opposite effects on lactate metabolism. The opposing metabolic actions, yet similar hemodynamic responses, of dichloroacetate and dobutamine suggest that these agents may be complementary in the treatment of congestive heart failure.

Dichloroacetic Acid↗
PubMed1994

Cyclosporine impairs release of endothelium-derived relaxing factors in epicardial and resistance coronary arteries.

BACKGROUND: Cyclosporin A is reported to impair endothelium-mediated vasorelaxation and induce endothelin release in some noncoronary vascular beds. We wished to determine whether acute cyclosporine administration induces endothelial dysfunction in coronary conductance or resistance arteries. METHODS AND RESULTS: We examined the effect of intracoronary acetylcholine, N omega-nitro-L-arginine methyl ester (L-NAME), L-arginine, nitroglycerin, and adenosine before and after acute cyclosporine administration (3 mg/kg IV over 30 minutes) in anesthetized dogs. Flow velocity was measured with a 0.014-in Doppler wire to assess resistance vessel responses, and epicardial coronary lumen area was simultaneously measured with a 4.3F, 30-MHz imaging catheter inserted over the Doppler wire. In 6 dogs, acetylcholine-induced increase in flow velocity was attenuated by cyclosporine in vehicle (137% to 55% at 10(-5) mol/L, P < .001), as was acetylcholine-induced epicardial vasodilation (14.1% to 6.7% at 10(-5) mol/L, P < .001). Vasodilation in response to intracoronary nitroglycerin (200 micrograms) and adenosine (6 mg) were unchanged by cyclosporine. Epicardial vasoconstriction with L-NAME (10(-4) mol/L) was reduced by cyclosporine (Pre, 7.4 +/- 0.9%; Post, 2.6 +/- 1.2%; P = .04), but L-arginine (10(-4) mol/L) had no effect after cyclosporine. In another 5 dogs, pure cyclosporine impaired acetylcholine-induced vasodilatation to the same degree as cyclosporine in vehicle (Cremophor); vehicle infusion did not impair endothelial function. In 5 more dogs, cyclosporine did not increase either arterial or coronary sinus concentrations of endothelin-1. CONCLUSIONS: The present study shows that cyclosporine acutely impairs release of endothelium-derived relaxing factor in canine conductance and resistance coronary arteries and provides evidence for decreased epicardial nitric oxide release after cyclosporine. The potential contribution of acute cyclosporine-induced coronary endothelial dysfunction to posttransplant vasculopathy needs further study.

Acetylcholine↗
PubMed1994

Evidence for the secretion of thyrotropin with enhanced bioactivity in syndromes of thyroid hormone resistance.

Resistance to thyroid hormone (RTH) is a rare genetic disorder associated with diverse mutations in the thyroid hormone receptor beta-gene. TSH-dependent thyroid hyperstimulation, leading to goiter and elevated thyroid hormone levels, is a characteristic feature of RTH. However, about 60% of untreated resistance patients have circulating TSH levels within the normal range, raising the possibility that the biological activity of TSH is altered. We, therefore, assayed the bioactivity of circulating TSH in 11 patients from 8 different kindreds with RTH, measuring cAMP production in Chinese hamster ovary cells transfected with the recombinant human TSH receptor as well as in FRTL-5 cells. The ratio of biologically active vs. immunoreactive TSH (B/I) was significantly higher in RTH patients than in 8 normal controls [TSH B/I, 4.2 +/- 0.9 (range, 2.2-11.9) vs. 1.3 +/- 0.2 (range, 0.6-2.1)]. TSH released in response to TRH had a bioactivity similar to that of circulating TSH under basal conditions. On the contrary, supraphysiological doses of T3 normalized the B/I ratio of circulating TSH. Concanavalin-A chromatography of TSH from RTH patients showed the presence of circulating forms with altered carbohydrate branching. Our data indicate that the bioactivity of circulating TSH in thyroid hormone resistance syndromes is enhanced and can be normalized after T3 administration. These findings may account for the occurrence of goiter and elevated thyroid hormone levels in RTH patients despite normal serum TSH concentrations.

Adult↗
PubMed1994

Nonglycoside inotropes in congestive heart failure. Are they beneficial or harmful?

Nonglycosidic adrenergic and nonadrenergic inotropic drugs improve systemic hemodynamics and left ventricular function in patients with severe congestive heart failure. As these beneficial effects are observed with short-term therapy, the use of these agents should be restricted to the treatment of acute heart failure. Long-term therapy with adrenergic agents as well as the phosphodiesterase inhibitors appears to enhance mortality in patients with chronic systolic heart failure. Potential indications for long-term therapy with nonglycosidic inotropic drugs include vesnarinone and ibopamine for selected patients with refractory heart failure or as pharmacologic bridges to cardiac transplantation.

Animals↗
PubMed1993

Assessment of left ventricular diastolic function in dilated cardiomyopathy with cine magnetic resonance imaging: effect of an angiotensin converting enzyme inhibitor, benazepril.

The effects of angiotensin converting-enzyme inhibitor, benazepril, on diastolic function in patients with dilated cardiomyopathy, with (n = 4) or without (n = 11) mitral regurgitation, were examined with the time-volume curve of the left ventricle derived from cine magnetic resonance images. Peak filling rate/end-systolic volume and ejection fraction were increased in the group without regurgitation (p < 0.01) but not in the group with regurgitation after treatment. There was a strong correlation between peak filling rate/end-systolic volume and ejection fraction (r = 0.89) and between the change in peak filling rate/end-systolic volume and that in ejection fraction after treatment (r = 0.74) in the group without regurgitation. These findings suggest that in some patients with dilated cardiomyopathy benazepril has favorable effects on diastolic function, which seem to be related to improvement in systolic function. This drug may not be as beneficial in patients with dilated cardiomyopathy complicated by mitral regurgitation.

Adult↗
PubMed1993

Assessment of coronary conductance and resistance vessel reactivity in response to nitroglycerin, ergonovine and adenosine: in vivo studies with simultaneous intravascular two-dimensional and Doppler ultrasound.

OBJECTIVES: The aim of this study was to determine the differential effects of nitroglycerin, ergonovine and adenosine on the resistance vessels in vivo by using a Doppler-tipped guide wire in combination with an ultrasound imaging catheter. BACKGROUND: Catheter-based two-dimensional intravascular ultrasound yields images of the coronary arteries from which cross-sectional areas can be measured. Intravascular Doppler ultrasound techniques allow measurement of coronary blood flow velocity. The simultaneous use of the two techniques can yield anatomic and physiologic information on conductance and resistance vessels but has not been tried in the coronary arteries. METHODS: In 15 dogs, we studied coronary flow and vascular reactivity in response to pharmacologic agents using two approaches: 1) a 30-MHz, 4.3F imaging catheter placed alongside a 0.018-in. (0.046 cm) Doppler wire in the circumflex or left anterior descending coronary artery (n = 5); 2) the ultrasound imaging catheter introduced directly over a 0.014-in. (0.036 cm) Doppler wire (n = 10). Vasodilator and vasoconstrictor responses were studied by using intracoronary nitroglycerin (50, 100 and 200 micrograms), ergonovine (200 micrograms) and adenosine (6 mg). RESULTS: Nitroglycerin caused a dose-dependent increase in epicardial coronary artery cross-sectional area and, to a lesser extent, in average peak flow velocity, resulting in an increase in volumetric coronary blood flow of 39% and 50% at the doses of 100 and 200 micrograms, respectively. With these doses of nitroglycerin, the decrease in diastolic to systolic velocity ratio and the increased change in cross-sectional area from end-diastole to end-systole suggested an enhanced epicardial coronary artery compliance. With ergonovine, a 12% reduction in epicardial coronary artery cross-sectional area was seen, without a significant change in average peak velocity, resulting in a 15% decrease in volumetric coronary blood flow. Adenosine caused a 270% increase in average peak velocity but no change in epicardial coronary artery cross-sectional area, resulting in a 270% increase in volumetric blood flow. CONCLUSIONS: This study demonstrates that nitroglycerin and ergonovine predominantly influence coronary conductance arteries whereas adenosine mainly dilates coronary resistance vessels. These findings also demonstrate that the combined use of a two-dimensional and a Doppler ultrasound transducer within one catheter assembly can provide information on the differential effects of vasoactive agents on the epicardial and microvascular coronary circulation.

Adenosine↗
PubMed1993

Importance of oxygen-haemoglobin binding to oxygen transport in congestive heart failure.

OBJECTIVE: To assess the importance of 2,3-diphosphoglycerate (2,3-DPG) and oxygen-haemoglobin binding to oxygen transport in patients with congestive heart failure. METHODS: In 30 patients with severe congestive heart failure, arterial, mixed venous, and coronary sinus venous blood concentrations of 2,3-DPG were measured and systemic output and coronary sinus blood flow were measured by a thermodilution technique. Oxygen-haemoglobin affinity was expressed as the oxygen tension in mm Hg at which blood is 50% saturated with oxygen (P50). RESULTS: Compared with normal values, 2,3-DPG was high in arterial blood (2.58 mumol/ml, p = 0.01; 20.8 mumol/g haemoglobin, p < 0.0001). Significant gradients between arterial, mixed venous, and coronary sinus blood 2,3-DPG concentrations were also found (mixed venous = 2.40 mumol/ml, p = 0.05 v arterial blood; coronary sinus venous blood = 2.23 mumol/ml, p < 0.04 v arterial blood). P50 was correspondingly high compared with the accepted normal value (mean 29.7 mm Hg, normal 26.6 mm Hg, p < 0.001). Systemic oxygen transport (351 ml O2/min/m2) varied directly with the forward cardiac index (r = 0.89, p < 0.0001). There was no relation between systemic oxygen transport and arterial oxygen content. Similarly, myocardial oxygen transport was found to vary directly with coronary sinus blood flow. Calculations of changes in cardiac index and coronary sinus blood flow at normal oxygen-haemoglobin binding indicate that a considerable increase in cardiac index and coronary blood flow would be required to maintain similar systemic and myocardial oxygen transport. CONCLUSIONS: In patients with severe heart failure increased 2,3-DPG and reduced oxygen-haemoglobin binding may be compensatory mechanisms that maintain adequate systemic and delivery of oxygen to myocardial tissue.

2,3-Diphosphoglycerate↗
PubMed1993

Effect of selective angiotensin II receptor antagonism and angiotensin converting enzyme inhibition on the coronary vasculature in vivo. Intravascular two-dimensional and Doppler ultrasound studies.

BACKGROUND: Although angiotensin converting enzyme (ACE) inhibitors have been reported to increase coronary blood flow, the effect of selective angiotensin II (AT1)-receptor antagonism on the coronary circulation has not been defined. METHODS AND RESULTS: We examined the effects of the AT1-receptor antagonist Losartan (DuP 753, 0.2-3.2 mg/kg) on coronary arteries in vivo in 11 dogs, using a combination of intravascular two-dimensional and Doppler ultrasound. In six dogs, a 30-MHz, 4.3F ultrasound imaging catheter was placed in the midsegment of the circumflex coronary artery to measure cross-sectional area (CSA), and a 0.018-in. Doppler wire was placed alongside to measure coronary flow velocity. At peak effect (1.6 mg/kg), Losartan increased mean coronary CSA from 7.9 +/- 0.5 to 9.5 +/- 0.8 mm2 and average peak velocity (APV) from 32 +/- 10 to 56 +/- 18 cm/sec, resulting in an increase in coronary blood flow from 74 +/- 19 to 151 +/- 36 mL/min. The maximal effect of the ACE inhibitor enalaprilat (5 mg) was an increase in CSA from 7.7 +/- 0.7 to 8.4 +/- 0.8 mm2 and an increase in APV from 36 +/- 10 to 53 +/- 20 cm/sec, with an increase in coronary blood flow from 82 +/- 25 to 122 +/- 41 mL/min. Relative to maximal hyperemia with adenosine (6 mg i.c.), the magnitude of flow increase from baseline was 0.37 with the AT1-receptor antagonist and 0.19 with the ACE inhibitor (p < 0.05). These effects were seen without changes in heart rate or systemic arterial pressure. In an additional five dogs, the ultrasound imaging catheter was introduced directly over a 0.014-in. Doppler wire, and the effects of indomethacin, propranolol, and N omega-nitro-L-arginine methylester (L-NAME) on the vasodilator effect of Losartan (1.6 mg/kg) were examined. Indomethacin and propranolol had no effect on Losartan-induced vasodilation, suggesting that it was not mediated via prostaglandins or beta-adrenoceptors. However, Losartan-induced epicardial vasodilation was partially inhibited by L-NAME, suggesting an action partly dependent on endothelial release of nitric oxide. CONCLUSIONS: Thus, these acute studies in anesthetized dogs suggest that inhibition of AT1-receptors in the coronary circulation results in vasodilator responses greater in magnitude than ACE inhibition and partly endothelium dependent. The exact role for AT1-receptors in human coronary physiology and pathology remains to be defined.

Adenosine↗
PubMed1993

Mechanical strain and collagen potentiate mitogenic activity of angiotensin II in rat vascular smooth muscle cells.

The effects of extracellular matrix proteins and mechanical strain on the mitogenic activity of angiotensins I and II (AI and AII) were examined in cultured rat vascular smooth muscle (VSM) cells. VSM cells on various extracellular matrices were exposed to AII (1 microM) for 48 h. On plastic, AII induced only a 1.6-fold increase in [3H]thymidine incorporation, but on fibronectin- or type I collagen-coated plastic, the response to AII was enhanced from two- to fourfold. On a type I collagen-coated silicone elastomer, to which mechanical strain was applied, [3H]thymidine incorporation dramatically increased to a maximum of 53-fold. Dup 753 (10(-5) M) blocked the AII-induced increase in DNA synthesis. AI also increased DNA synthesis in VSM cells, and this response was also enhanced by mechanical strain. Mitogenic activity of AI was blocked by ramiprilat (10(-5) M), indicating that its mitogenic activity was via conversion to AII. The synergy between AII and strain was completely eliminated by neutralizing antibodies to PDGF AB (3 micrograms/ml). Furthermore, the mitogenic effect of AII in unstrained cells was also synergistic with submaximal concentrations of PDGF AB (1 ng/ml). Thus, the synergy between AII and mechanical strain probably results from synergism between AII and PDGF secreted in response to strain.

Angiotensin II↗
PubMed1993

Effects of trichloroethylene anaesthesia on salivary paracetamol elimination.

The effect of trichloroethylene (Trielene) anaesthesia was studied in 10 young male patients undergoing short surgical procedures. Equal number of males operated upon for the same indication under epidural anaesthesia, served as a control group. Paracetamol concentrations in saliva were measured at hourly intervals on the day before and after surgery. Paracetamol half life (t1/2) significantly decreased (from 2.5 to 0.84 h) and clearance rate (CL) significantly increased (from 8.0 to 14.0 ml/min/kg) as compared to preoperative values. The control also showed significant but smaller alterations in these parameters. Our result suggests that trielene exposure may accelerate the hepatic metabolism of paracetamol.

Acetaminophen↗
PubMed1992

Systemic and coronary hemodynamic effects of bepridil in patients with depressed left ventricular function.

To assess the effects of oral bepridil therapy (10-14 days) on cardiac performance and myocardial energetics in the presence of depressed left ventricular function, systemic and coronary hemodynamic effects and neurohumoral effects were evaluated in 7 patients with coronary artery disease and reduced ejection fraction at control, submaximal, and maximal pacing rates during atrial pacing stress. After bepridil therapy, arterial, right atrial, and left ventricular filling pressures as well as systemic vascular resistance and left ventricular stroke work index did not change, suggesting no deleterious effects of bepridil on cardiac performance in patients with reduced ejection fraction. Rate-pressure product, myocardial oxygen consumption, coronary sinus blood flow, myocardial lactate extraction, and catecholamine balance remained unchanged. Development of angina during pacing showed a variable response to bepridil. We conclude that despite its potential negative inotropic effect, bepridil does not exert deleterious effects on hemodynamics or left ventricular performance. The mechanism for its beneficial antianginal effect may be due to favorable redistribution of myocardial blood flow to ischemic zones; no clear effect on anginal threshold or sympathetic tone could be demonstrated in these patients.

Aged↗