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Giris Jacob

Publications and source records attributed to Giris Jacob.

At least 19 recordsLinked to original sources
PubMed2006

Effect of aging on the cardiovascular regulatory systems in healthy women.

Aging, independently from the hormonal status, is a major risk factor for cardiovascular morbidity in healthy women. Therefore, we studied the effect of healthy aging on the cardiovascular homeostatic mechanisms in premenopausal and postmenopausal women with similar estrogen levels. Twelve healthy postmenopausal women, confirmed by follicular-stimulating hormone (FSH) and luteal hormone (LH) levels, were compared with 14 normally menstruating women during the early follicular phase (young-EF), to avoid as much as possible the effects of estrogen. Systolic BP was 108 +/- 1.5 vs. 123 +/- 2.5 (P < 0.001), supine norepinephrine was 260 +/- 30 vs. 216 +/- 45 and upright 640 +/- 100 vs. 395 +/- 50 pg/ml (P = 0.05) in young-EF vs. postmenopausal, respectively. Plasma renin activity and aldosterone remained unchanged. Vagal cardiac tone indices decreased significantly with aging (young-EF vs. postmenopausal): high-frequency (HF) band, root mean square successive differences (rMSSD) and proportion of R-R intervals >50 ms (PNN50%) were 620 +/- 140 vs. 270 +/- 70 (P = 0.04), 53 +/- 7 vs. 30 +/- 3 (P = 0.02), and 23 +/- 5 vs. 10 +/- 3 (P = 0.04), respectively. LF to HF ratio was 0.85 +/- 0.17 in young-EF and became 1.5 +/- 0.22 in postmenopausal (P = 0.03). Both arms of the baroreflex, +BRS (29 +/- 5 vs. 13.5 +/- 2.5, P = 0.01) and -BRS (26 +/- 4 vs. 15 +/- 1.5, P = 0.02) decreased with aging. Cardiovascular alpha(1)-adrenoreceptor responsiveness significantly increased and beta-decreased in postmenopausal compared with young EF (P < 0.001, both). The corrected QT intervals (QTc) were similar, whereas corrected JT intervals (JTc) and JTc to QTc ratio were prolonged in the postmenopausal group. We conclude that in young women, parasympathetic control is the main regulator of the cardiovascular system and in postmenopausal women, sympathetic tone dominates. The transition from parasympathetic to sympathetic control may contribute to the increased cardiovascular morbidity with aging.

Adult↗
PubMed2006

Impaired cerebral CO2 vasoreactivity: association with endothelial dysfunction.

Conflicting data exist on the role of nitric oxide (NO) in cerebral blood flow (CBF) autoregulation. Previous studies involving human and animal subjects seem to indicate that NO involvement is limited to the CO(2)-dependent mechanism (chemoregulation) and not to the pressure-dependent autoregulation (mechanoregulation). We tested this hypothesis in patients with impaired endothelial function compared with healthy controls. Blood pressure, heart rate, end-tidal Pco(2), CBF velocities (CBFV), forearm blood flow, and reactive hyperemia were assessed in 16 patients with diabetes mellitus and/or hypertension and compared with 12 age- and sex-matched healthy controls. Pressure-dependent autoregulation was determined by escalating doses of phenylephrine. CO(2) vasoreactivity index was extrapolated from individual slopes of mean CBFV during normocapnia, hyperventilation, and CO(2) inhalation. Measurements were repeated after sodium nitroprusside infusion. Indexes of endothelial function, maximal and area under the curve (AUC) of forearm blood flow (FBF) changes, were significantly impaired in patients (maximal flow: 488 +/- 75 vs. 297 +/- 31%; P = 0.01, AUC DeltaFBF: 173 +/- 17 vs. 127 +/- 11; P = 0.03). Patients and controls showed similar changes in cerebrovascular resistance during blood pressure challenges (identical slopes). CO(2) vasoreactivity was impaired in patients compared with controls: 1.19 +/- 0.1 vs. 1.54 +/- 0.1 cm.s(-1).mmHg(-1); P = 0.04. NO donor (sodium nitroprusside) offsets this disparity. These results suggest that patients with endothelial dysfunction have impaired CO(2) vasoreactivity and preserved pressure-dependent autoregulation. This supports our hypothesis that NO is involved in CO(2)-dependent CBF regulation alone. CBFV chemoregulation could therefore be a surrogate of local cerebral endothelial function.

Brain↗
PubMed2006

Beta2-adrenoceptor genotype and function affect hemodynamic profile heterogeneity in postural tachycardia syndrome.

Previous studies suggest that the beta2-adrenoceptor functions abnormally in patients with postural tachycardia syndrome (POTS) and may contribute to their altered hemodynamic profile. To test the hypothesis that the beta2-adrenoceptor response is decreased in POTS, we studied: (1) the arterial vasodilation response to the beta agonist, isoproterenol, and (2) the distribution of common polymorphisms (codons 16 and 27) of the gene coding the receptor (beta2-AR) in a large population with POTS. We measured plasma catecholamines and monitored hemodynamics and changes in forearm and leg blood flow to incremental doses of intraarterial isoproterenol in 9 patients with POTS compared with 8 healthy subjects. For polymorphism assessment we collected DNA from 57 patients with POTS and compared with 67 age-sex matched healthy subjects. Circulating catecholamines were significantly higher in POTS subjects compared with controls. Intrabrachial and intrafemoral isoproterenol infusion elicited a dose-dependent increase in blood flow. In healthy subjects, blood flow increased (mean+/-SEM) 400+/-70% in the forearm and 170+/-40% in the leg, but only 280+/-60% in forearms and 120+/-20% in legs of patients with POTS (ANOVA for both P<0.001). The genotype and allele distributions for codons 16 and 27 beta2-AR variants were not different in the 2 groups. However, the blood pressure and plasma norepinephrine levels diverged in patients according to their genotype. Patients with Gly16Gly and patients with Glu27Glu had lower plasma catecholamines and higher supine and upright blood pressure, compared with other genotypes. Therefore, both decreased beta2-adrenoceptor-related vasodilation and beta2-AR polymorphisms may contribute to the hemodynamic diversity of patients with POTS.

Adrenergic beta-Agonists↗
PubMed2006

Physiological and catecholamine response to sympathetic stimulation in turner syndrome.

OBJECTIVE: Women with Turner syndrome have increased heart rate and high blood pressure (BP), and have been described as having high tolerance for emotional stress. We hypothesized that women with Turner syndrome have reduced catecholaminergic and physiological response to sympathetic stimulation, and that changes in BP and heart rate are related to their catecholamine response to sympathetic stimulation. DESIGN AND PATIENTS: Ten young women with Turner syndrome, age 17-34 years were the subjects of this study. Their response to sympathetic stimulation was compared to a group of 10 age-matched healthy women. MEASUREMENTS: After a period of 30 min resting, subjects and controls were subjected to an escalating series of sympathetic stimulation: orthostatic, cold pressor and exercise, and their plasma catecholamines and haemodynamic response were monitored and compared to resting levels. RESULTS: Resting heart rate was higher in Turner syndrome patients at 83 +/- 9 beats per min (bpm, mean +/- SD), as compared to controls (74 +/- 10 bpm, P < 0.05). Their supine BP was also higher at 122 +/- 9/84 +/- 6 vs. 106 +/- 11/70 +/- 9 mmHg (P < 0.02/< 0.02). The corresponding resting norepinephrine, but not epinephrine, was higher in Turner syndrome patients (2.54 +/- 1.09 nmol/l) as compared to controls (1.69 +/- 0.55 nmol/l, P < 0.02). In response to orthostatic stimulation and cold pressor test the systolic, but not the diastolic BP or heart rate, increased in Turner syndrome patients but not in the control group (P < 0.01). The change in blood catecholamine levels was comparable in both groups. Their physiological response to exercise was normal. Yet, the exercise-induced surge of norepinephrine and epinephrine in Turner syndrome patients was lower (P < 0.02). CONCLUSIONS: Turner syndrome is associated with dysregulation of the sympathetic nervous system (SNS), leading to tachycardia and high BP, increased resting norepinephrine levels, and a greater tolerance of the cathecholamine response to exercise.

Adolescent↗
PubMed2006

The importance of recognizing postural pseudoanemia.

The determination of the packed red cell volume and the hemoglobin level has been paramount for monitoring anemia and blood loss for patients in the hospital setting. Recently, these variables have been studied during various control conditions including changes in posture. It has been found that the hematocrit changes markedly with alteration of body posture, in such a way that shifts of estimated blood volume of 1 pint can commonly be elicited by a simple change of posture from supine to upright or vice versa. Therefore, it is important to recognize that in addition to the numerous pathological conditions that may affect the value of the packed cell volume, certain physiological maneuvers may have an equal impact and may confound the accurate assessment of true pathological changes in these variables. Thus, changes in posture can lead to substantial changes in hematocrit, which may be attributed mistakenly to blood loss or acute anemia and may result in a cascade of unnecessary diagnostic costs. In reality, these changes represent postural pseudoanemia, a normal physiological response to a change in position from standing to lying.

Adult↗
PubMed2005

Fever due to aortitis.

We report a case of vasculitis with predominant aortic involvement. Vasculitis of large vessels has a limited number of tools for diagnosis and follow-up. A 78-year-old woman was referred to the internal medicine department with a 2-month history of fever of unknown origin (FUO), night sweats, weight loss and markedly elevated ESR and CRP. The results of an extended routine investigation found no infection, malignancy, hypersensitivity or autoimmune disorder. The patient did not suffer from claudication; systolic blood pressure difference between arms was 20 mm Hg. Temporal artery biopsies were negative. 2-18F-Fluorine-2-deoxy-D -glucose positron emission tomography (FDG PET) scan imaging demonstrated intense FDG uptake along the aorta and in the brachio-cephalic and carotid arteries consistent with arteritis. A high dose of corticosteroid therapy (1 mg/kg) was instituted with further tapering. The therapy was followed by complete resolution of the symptoms and pathological FDG uptake on repeated FDG PET. Second-line therapy was not added because of positive conversion of Mantaux test followed by rifampicin prophylaxis. FDG PET should be a part of the work-up of FUO when routine investigation fails to determine its etiology. FDG PET is useful both for diagnosis and assessment of response to therapy for large-vessel vasculitis.

Aged↗
PubMed2005

Tyramine-induced vasodilation mediated by dopamine contamination: a paradox resolved.

We reported previously that intravenous administration of tyramine induced a paradoxical forearm vasodilation and an increase in plasma dopamine, raising the possibility that dopamine is released by or converted from tyramine in vivo. Alternatively, tyramine can be nonenzymatically oxidized into dopamine in vitro, and this contamination may be responsible for the increase in plasma dopamine and forearm vasodilation. To distinguish between these possibilities, we measured the hemodynamic and neurohumoral effects of an intravenous infusion of a specially prepared dopamine-free tyramine solution in 8 normal volunteers at a dose that increased systolic blood pressure by approximately 25 mm Hg (from 107+/-5 to 133+/-5 mm Hg; P <0.001) and compared it with an equivalent dose of norepinephrine. Tyramine increased plasma norepinephrine (139+/-18 to 226+/-30 pg/mL; P <0.02), its intraneuronal metabolite dihydroxyphenylglycol (980+/-73 to 2245+/-206 pg/mL; P <0.001), and systemic vascular resistance, but not plasma dopamine or its intraneuronal metabolite dihydroxyphenylacetic acid. Tyramine and norepinephrine produced nonsignificant increases in forearm vascular resistance. We conclude that tyramine-induced forearm vasodilation reported in previous studies is explained by the presence of dopamine contamination in tyramine preparations. Intravenous administration of dopamine-free tyramine and norepinephrine produced equivalent systemic vasoconstriction. The forearm vasculature was not useful in monitoring the vasoconstrictive effects of either agent. The possibility of dopamine contamination needs to be considered when interpreting previously published studies using tyramine as a pharmacological tool to assess sympathetic function, and it must be avoided in future studies.

Adult↗
PubMed2005

A new clinical method for the assessment of penile endothelial function using the flow mediated dilation with plethysmography technique.

PURPOSE: Penile endothelial function (EnF) is 1 of the major factors involved in the pathophysiology of erectile dysfunction. EnF assessment could offer crucial information on the etiology and degree of severity of cavernosal vascular pathology. In the present study we propose a new technique for the evaluation of penile EnF and test its applicability using strain gauge plethysmography. MATERIALS AND METHODS: A total of 23 healthy subjects (13 younger and 10 older than 40 years) with no history of erectile dysfunction were studied. The flow mediated dilation technique was applied to the arm and penis in both age groups for the assessment of EnF. Baseline blood flow and the sequential flow recordings after rapid cessation of 5 minutes of ischemia were obtained in both organs. RESULTS: Baseline flow in the penis was significantly higher (approximately 3-fold) than that in the forearm and was not affected by age in either organ. Both measures of penile EnF, ie area under the flow-time curve (AUC) and maximal flow obtained after ischemia were significantly lower in the older group compared to the younger group (p <0.01 and p <0.02, respectively). Individual penile AUC and maximal flow were significantly correlated with age (r = 0.55, p <0.01 and r = 0.50, p <0.02, respectively). Finally a positive, significant correlation existed between penile and forearm AUC (p <0.05, r = 0.48). CONCLUSIONS: The implementation of the flow mediated dilation technique using mercury strain gauge plethysmography is simple and applicable for the assessment of penile EnF. Endothelial function parameters in the penis were found to correlate with those in the forearm, thus support for the validity of the technique is given. Further strength for the validity of this procedure in the penis comes from the comparison between the forearm and penis, and the relation to subject age.

Adult↗
PubMed2005

Postural pseudoanemia: posture-dependent change in hematocrit.

OBJECTIVE: To determine the magnitude of posture-related changes in blood components. SUBJECTS AND METHODS: Twenty-eight healthy subjects were studied between 1995 and 2004 at the Vanderbilt Autonomic Dysfunction Center, Nashville, Tenn. Lying and standing plasma volume (PV) and hematocrit (Hct) values were determined for each subject. RESULTS: Individual PV decreases on standing ranged from 6% to 25%. The absolute mean +/- SD PV shift was 417+/-137 mL (range, 149-717 mL). The mean +/- SD change in Hct was from 37.7%+/-2.8% while supine to 41.8%+/-3.2% within 30 minutes of standing. This absolute increase in Hct of 4.1%+/-1.3% represents a relative increase of 11.0%+/-3.6% from lying to standing. CONCLUSIONS: Changes in posture can lead to substantial changes in Hct, which may be attributed mistakenly to blood loss or acute anemia and result in a cascade of unnecessary diagnostic costs. In reality, these changes represent postural pseudoanemia, a normal physiological response to a change in position from standing to lying (and vice versa).

Adult↗
PubMed2003

Neurovascular dissociation with paradoxical forearm vasodilation during systemic tyramine administration.

BACKGROUND: Despite the widespread use of tyramine as a pharmacological tool to assess the effects of norepinephrine release from sympathetic nerve terminals, its vascular effects are not adequately characterized. In particular, previous results indicate that intravenous tyramine produces little if any systemic vasoconstriction, suggesting that tyramine does not cause significant norepinephrine release from sympathetic nerves innervating peripheral vascular beds. To test this hypothesis, we determined the effects of intravenous tyramine on local forearm norepinephrine spillover and vascular resistance. METHODS AND RESULTS: Seven healthy subjects were studied with systemic and local forearm norepinephrine spillover and forearm blood flow at baseline, during systemic tyramine infusion, and after sympathetic stimulation induced by the cold pressor test. Tyramine infusion caused a significant increase in systemic and forearm norepinephrine spillover. The amount of norepinephrine released into the forearm by tyramine was similar to that caused by cold pressor stimulation, 0.15+/-0.05 versus 0.18+/-0.05 ng x dL(-1) x min(-1). As expected, forearm vascular resistance increased during the cold pressor test, but tyramine produced forearm vasodilation (4.5+/-1 versus -5+/-1 mm Hg x dL(-1) x min(-1), P<0.03) despite the increase in local norepinephrine spillover. In 6 additional subjects, plasma dopamine increased significantly during tyramine administration, from 11+/-3 to 662+/-105 pg/mL. CONCLUSIONS: Thus, systemic tyramine infusion evokes a significant increase in peripheral norepinephrine spillover, and this, paradoxically, is associated with local vasodilatation rather than vasoconstriction.

Adult↗
PubMed2003

Role of nitric oxide in the regulation of cerebral blood flow in humans: chemoregulation versus mechanoregulation.

BACKGROUND: From animal studies it emerged that nitric oxide is important for the modulation of CO2-mediated cerebral blood flow (CBF chemoregulation) but not for the pressor-dependent mechanism (mechanoregulation). This hypothesis was tested in 18 healthy subjects. METHODS AND RESULTS: Peak velocity (PV), diastolic velocity (DV), and mean velocity (MV) were measured by transcranial Doppler of the middle cerebral artery. Chemoregulation was assessed during normocapnia, hypocapnia, and after inhaled mixture of 95% O2+5% CO2. Mechanoregulation was evaluated by incremental doses of phenylephrine. Measurements were repeated during infusion of sodium nitroprusside (SNP). Regional cerebrovascular resistance (CVR) was calculated as mean blood pressure (BP)/MV. SNP infusion decreased mean BP by 7 mm Hg and CVR decreased from 1.38+/-0.08 to 1.29+/-0.09 mm Hg/cm x s(-1); P=0.01, resulting in unaffected CBF. Phenylephrine (25 to 250 microg) caused a similar increase in BP in a dose-response fashion before and during SNP infusion. Despite the increments in BP and CVR, CBF remained unaffected. During hyperventilation (end-tidal CO2 approximately 24 mm Hg), CVR increased by 75+/-3% and PV and DV decreased by 27+/-2% and 43+/-2%, respectively (P<0.001 for all). SNP infusion blunted the vasoconstrictive effect of hypocapnia; CVR increased only by 57+/-5%, and PV and DV decreased by 23+/-2% and 35+/-3%, respectively, (P<0.05 for all). Similarly, SNP augmented the vasodilatory effect of hypercapnia. CONCLUSIONS: Exogenous nitric oxide donor affects the basal cerebral vascular tone without affecting the CBF mechanoregulation. However, it selectively affects only the chemoregulatory mechanism (CO2-dependent). Thus, the CO2-NO axis is a cardinal pathway for CBF regulation in humans.

Adrenergic alpha-Agonists↗
PubMed2003

Hereditary dysautonomias: current knowledge and collaborations for the future.

The hereditary dysautonomias (H-Dys) are a large group of disorders that affect the autonomic nervous system. Research in the field of H-Dys is very challenging, because the disorders involve interdisciplinary, integrative, and "mind-body" connections. Recently, medical scientists, NIH/NINDS representatives, and several patient support groups gathered for the first time in order to discuss recent findings and future directions in the H-Dys field. The H-Dys workshop was instrumental in promoting interactions between basic science and clinical investigators. It also allowed attendees to have an opportunity to meet each other, understand the similarities between the various forms of dysautonomia, and experience the unique perspective offered by patients and their families. Future advances in H-Dys research will depend on a novel multi-system approach by investigators from different medical disciplines, and it is hoped that towards a common goal, novel "bench-to-bedside" therapeutics will be developed to improve the lives of, or even cure, patients suffering from dysautonomic syndromes.

Animals↗
PubMed2003

Dysautonomia in the joint hypermobility syndrome.

PURPOSE: Extraarticular manifestations of the joint hypermobility syndrome may include the peripheral nervous system. The purpose of this study was to investigate autonomic function in patients with this syndrome. METHODS: Forty-eight patients with the joint hypermobility syndrome who fulfilled the 1998 Brighton criteria and 30 healthy control subjects answered a clinical questionnaire designed to evaluate the frequency of complaints related to the autonomic nervous system. Next, 27 patients and 21 controls underwent autonomic evaluation: orthostatic testing, cardiovascular vagal and sympathetic functions, catecholamine levels, and adrenoreceptor responsiveness. RESULTS: Symptoms related to the autonomic nervous system, such as syncope and presyncope, palpitations, chest discomfort, fatigue, and heat intolerance, were significantly more common among patients. Orthostatic hypotension, postural orthostatic tachycardia syndrome, and uncategorized orthostatic intolerance were found in 78% (21/27) of patients compared with in 10% (2/21) of controls. Patients with the syndrome had a greater mean (+/- SD) drop in systolic blood pressure during hyperventilation than did controls (-11 +/- 7 mm Hg vs. -5 +/- 5 mm Hg, P = 0.02) and a greater increase in systolic blood pressure after a cold pressor test (19 +/- 10 mm Hg vs. 11 +/- 13 mm Hg, P = 0.06). Patients with the syndrome also had evidence of alpha-adrenergic (as assessed by administration of phenylephrine) and beta-adrenergic hyperresponsiveness (as assessed by administration of isoproterenol). CONCLUSION: The autonomic nervous system-related symptoms of the patients have a pathophysiological basis, which suggests that dysautonomia is an extraarticular manifestation in the joint hypermobility syndrome.

Adolescent↗
PubMed2003

Unusual cause of partially reversible severe cardiovascular autonomic failure.

We report an unusual case of partially reversible severe cardiovascular autonomic system failure in a patient with double primary malignancies. The patient presented with severe orthostatic hypotension preceding the detection of lymphoma and lung cancer. The patient had autonomic failure on presentation. One year after surgery and chemotherapy, there was a gradual improvement in both symptoms and autonomic function simultaneously. We conclude that paraneoplastic severe autonomic failure can be reversible.

Autonomic Nervous System↗
PubMed2003

Spectrum of autonomic cardiovascular neuropathy in diabetes.

OBJECTIVE: Diabetic patients with incapacitating orthostatic hypotension can have either a "hyperadrenergic" or "hypoadrenergic" presentation. Although the latter is related to overt autonomic neuropathy, the former is proposed to be explained by appropriate autonomic responses. We hypothesize, however, that both conditions are part of a spectrum of autonomic dysfunction. RESEARCH DESIGN AND METHODS: We studied 16 consecutive diabetic patients with preserved renal function referred for incapacitating orthostatic hypotension and characterized their autonomic and neurohumoral cardiovascular regulation. RESULTS: Six patients had a hyperadrenergic orthostatic response: systolic blood pressure fell 42 +/- 15 mmHg, heart rate increased 20 +/- 3 bpm, and plasma norepinephrine increased from 340 +/- 80 to 910 +/- 100 pg/ml. Ten patients had a hypoadrenergic response: systolic blood pressure fell 78 +/- 5 mmHg, heart rate increased only 7 +/- 3 bpm, and norepinephrine increased only from 130 +/- 28 to 230 +/- 40 pg/ml. Vagal (sinus arrhythmia, Valsalva ratio) and sympathetic (response to hyperventilation, postprandial hypotension) responses were impaired in both groups, but to a greater extent in the hypoadrenergic group. Notwithstanding severe orthostatic hypotension, the postural increase in plasma renin was blunted in both groups, more so in the hypoadrenergic group. Despite preserved renal function, patients had mild anemia due to impaired erythropoietin release, as seen in primary cases of autonomic failure. CONCLUSIONS: Our results suggest that diabetic patients presenting with hyperadrenergic orthostatic hypotension have an initial stage of autonomic neuropathy, with overtly abnormal vagal function and early signs of sympathetic impairment. Furthermore, altered renin response can contribute to the patients' orthostatic hypotension.

Arrhythmias, Cardiac↗
PubMed2002

Fatal acute myocardial infarction during severe thrombocytopenia in a patient with idiopathic thrombocytopenic purpura.

Because platelets play a major role in most thrombotic events, it is not surprising that all cases of myocardial infarctions in patients with idiopathic thrombocytopenic purpura (ITP) have been reported to occur only when platelets counts begin to rise. We report on a 69-year-old man with ITP who had acute myocardial infarction while he was severely thrombocytopenic (2000/microL). We hypothesize that the pathogenesis of myocardial infarction in thrombocytopenic patients with ITP may result from endothelial damage induced by autoantibodies directed against antigens present on both platelets and coronary endothelial cells.

Aged↗