Search PubMed⌕ Search

Biomedical subjects

D M Kaye

Publications and source records attributed to D M Kaye.

61 records · Page 4Linked to original sources
PubMed1994

Heart rate spectral analysis, cardiac norepinephrine spillover, and muscle sympathetic nerve activity during human sympathetic nervous activation and failure.

BACKGROUND: Although heart rate variability (HRV) at 0.1 Hz has been proposed as a noninvasive clinical measure of cardiac sympathetic nerve firing, this premise has not been sufficiently validated by comparison with techniques such as microneurography and the measurement of norepinephrine spillover from the heart that more directly reflect presynaptic sympathetic activity. METHODS AND RESULTS: We compared the three techniques under conditions of effective cardiac sympathetic denervation, pure autonomic failure (n = 4), dopamine beta-hydroxylase deficiency (n = 1), and after cardiac transplantation (n = 9) as well as in the context of sympathetic nervous activation in cardiac failure (n = 15) and with aging (n = 10). Age-matched comparisons were made in each case with healthy individuals drawn from a pool of 52 volunteers. In pure autonomic failure and early after transplantation, cardiac norepinephrine spillover was negligible, and HRV was low. Late after transplantation, however, cardiac norepinephrine spillover returned to normal levels, and HRV remained low. In comparison to younger subjects (18 to 35 years old), older individuals (60 to 75 years old) had higher muscle sympathetic nerve activity (young, 22.9 +/- 1.9; old, 31.3 +/- 5.8 bursts per minute; P < .05) and cardiac norepinephrine spillover (young, 14.3 +/- 2.5; old, 20.1 +/- 3.0 ng/min; P < .05). In contrast, total HRV was reduced by 89%, and at 0.1 Hz it was reduced by 93% (P < .05). Cardiac failure was also characterized by elevated cardiac norepinephrine spillover (cardiac failure patients, 59 +/- 4; healthy volunteers, 18 +/- 3 ng/min; P < .01) but reduced 0.1 Hz HRV (cardiac failure patients, 49 +/- 17; healthy volunteers, 243 +/- 4 ms2; P < .05). CONCLUSIONS: HRV at 0.1 Hz depends on factors in addition to cardiac sympathetic nerve firing rates, including multiple neural reflexes, cardiac adrenergic receptor sensitivity, postsynaptic signal transduction, and electrochemical coupling, and is not directly related to cardiac norepinephrine spillover, which is a more direct measure of the sympathetic nerve firing rate.

Adolescent↗
PubMed1994

Monoaminergic neuronal activity in subcortical brain regions in essential hypertension.

In this study we aimed to elucidate the role of central noradrenergic, dopaminergic, adrenergic and serotonergic neuronal systems in the development of essential hypertension. Fifteen untreated essential hypertensive subjects (aged 44 +/- 3 years) and 32 healthy volunteers (aged 38 +/- 3 years) participated in this study. By combining direct blood sampling techniques with cerebral blood flow scans we were able to differentiate between cortical and subcortical venous drainage of the brain. Veno-arterial MHPG, HVA and 5-HIAA plasma concentration gradients combined with internal jugular vein plasma flows were used, according to the Fick Principle, to derive metabolite spillovers which in turn were used as indicators of central noradrenergic, dopaminergic and serotonergic neuronal activity, respectively. These amine systems, in both the brainstem and forebrain, have been implicated in the regulation of sympathetic outflow and blood pressure. Total body noradrenaline spillover to plasma was concurrently measured to assess the relationship between central monoamine turnover and sympathetic activity. Compared to their healthy counterparts the hypertensive subjects had an elevated release of MHPG from subcortical brain regions (1.4 +/- 0.3 v 0.5 +/- 0.2 nmol/min, p < 0.05). An inverse relationship between blood pressure and subcortical HVA overflow existed, with the HVA overflow being significantly lower in the hypertensives (0.5 +/- 0.2 v 2.1 +/- 0.5 nmol/min, p < 0.05). Subcortical 5-HUAA overflow did not differ between the two groups, and adrenaline spillover from the brain was not detected in either group. Subcortical MHPG overflow was significantly correlated with total body NA spillover to plasma (p < 0.05). These results indicate that reciprocal aberrations in subcortical noradrenaline and dopamine turnover exist in essential hypertension. Although the physiological significance of this remains to be unequivocally elucidated we postulate that elevated subcortical noradrenergic activity, presumably in the forebrain where noradrenergic neurons are pressor, may cause sympathoexcitation and play a role in the development of essential hypertension.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Impaired contraction and relaxation in skin resistance arteries from patients with congestive heart failure.

OBJECTIVE: The aim was to determine the pharmacological reactivity of human small resistance arteries in patients with cardiac failure. METHODS: Small arteries (< 300 microns internal diameter) were removed from gluteal skin biopsy specimens and mounted in a double myograph for isometric force recording. RESULTS: Arteries from six patients with congestive heart failure contracted to only 65% of the maximum response recorded in nine arteries from normal volunteers when activated by potassium chloride (124 mM), noradrenaline (1 microM), or both. The lesser contraction in congestive heart failure vessels with no significant shift in sensitivity (EC50) was also observed in concentration-response studies with noradrenaline, angiotensin I, and angiotensin II. The concentration-contraction curves for serotonin showed only 40% of the maximum contractility to K+ in normal arteries, and this ratio was similar in congestive heart failure arteries. Normal arteries precontracted with noradrenaline (1 microM) relaxed in response to sodium nitroprusside, calcitonin gene related peptide, and the endothelium dependent agonist acetylcholine; in congestive heart failure vessels there was a marked loss of the relaxation response only to acetylcholine. CONCLUSIONS: These results suggest that in chronic congestive heart failure skin resistance arteries have impaired contraction responses probably independent of any receptor down regulation. The loss of endothelium dependent vasodilatation to acetylcholine suggests that EDRF release is impaired. These changes may well play an important role in the disturbances of peripheral vascular function associated with heart failure.

Aged↗
PubMed1993

Functional and neurochemical evidence for partial cardiac sympathetic reinnervation after cardiac transplantation in humans.

BACKGROUND: The presence of cardiac reinnervation in humans after cardiac transplantation has been widely debated, based on the application of differing methods for the assessment of neuronal function. Some of these techniques have been rather indirect; consequently, the time course and extent of cardiac reinnervation remains uncertain. METHODS AND RESULTS: To test for the presence of cardiac reinnervation after transplantation, we examined neurochemical (radiolabeled norepinephrine [NE] kinetics) and functional markers (power spectral analysis, heart rate response to exercise) of cardiac sympathetic nerve integrity in 15 cardiac transplantation recipients and 25 healthy control subjects of similar age. Cardiac transplantation subjects were studied 9 weeks to 8 years after cardiac transplantation (10 "early" patients < 18 months and 5 "late" patients > 2 years after cardiac transplantation). At rest, cardiac NE spillover was markedly attenuated early after transplantation (11.2 +/- 18.3 pmol/min) compared with subjects late after transplantation (105 +/- 11 pmol/min, P < .01) or in healthy control subjects (103 +/- 15 pmol/min, P < .01). Heart rate variability (measured by total spectral power) was significantly reduced in cardiac transplantation recipients compared with control subjects (59.4 +/- 30 vs 1673 +/- 516 milliseconds squared; P < .05), with evidence of a trend toward increasing spectral power late after transplantation. During exercise, the cardiac NE spillover was significantly lower in early cardiac transplantation recipients when compared with control subjects (163 +/- 50 vs 1876 +/- 418 pmol/min, P < .01). Late cardiac transplantation subjects showed a response intermediate (1080 +/- 254 pmol/min) between that of the early cardiac transplantation and control groups. However, measurements of the neuronal reuptake process for NE (assessed by the fractional extraction of plasma labeled NE across the heart and tritiated dihydroxyphenylglycol release) were significantly depressed in both early and late cardiac transplantation subjects. CONCLUSIONS: The present study demonstrates a partial restoration of cardiac sympathetic nerve function in humans up to 8 years after heart transplantation.

Blood Pressure↗
PubMedDate not supplied

Central nervous system noradrenergic control of sympathetic outflow in normotensive and hypertensive humans.

We applied transmitter washout methodology, sampling internal jugular venous plasma via a percutaneously placed catheter, to study CNS norepinephrine release in humans and its relation to peripheral sympathetic activity. Norepinephrine overflows into the venous drainage of the brain, as do its precursor, DOPA, and metabolites DHPG and MHPG, indicating that the blood-brain barrier provides an incomplete impediment to their outward flux from the brain. Pharmacological testing with two drugs which altered CNS norepinephrine turnover, the tricyclic antidepressant desipramine and the ganglionic blocker, trimethaphan, demonstrated a direct relation existed between CNS norepinephrine release and sympathetic nerve firing rates. In essential hypertension, the sympathetic activation commonly present was associated with, and possibly caused by increased CNS release of norepinephrine, manifested in elevated overflow of norepinephrine, MHPG and DHPG from the brain. Bilateral jugular sampling, coupled with a cerebral venous sinus scan to delineate the drainage pattern, demonstrated that this increased norepinephrine release was confined to subcortical forebrain regions.

Blood Pressure↗
PubMedDate not supplied

Value of postoperative assessment of cardiac allograft function by transesophageal echocardiography.

Heart transplantation now provides an acceptable therapy for patients with severe end-stage heart disease. Although patient outcome has significantly improved both early and late after heart transplantation, early morbidity and mortality continues to affect overall survival and may be unpredictable. In an attempt to identify factors that may assist in predicting early outcome after orthotopic heart transplantation, we assessed allograft function in 16 patients in the immediate postoperative period, 30 minutes after weaning from cardiopulmonary bypass by measuring the fractional shortening of the left ventricle with transesophageal echocardiography. In addition, standard hemodynamic indexes of allograft function (arterial blood pressure, pulmonary capillary wedge pressure, mean pulmonary artery pressure, and cardiac output) were obtained at this early time point. Early outcome was assessed by the duration and peak dose of inotrope support required after transplantation, requirement for mechanical support, and the duration of stay in the intensive care unit. Left ventricular fractional shortening 30 minutes after cardiopulmonary bypass was significantly lower in those patients requiring inotropic support (28.4% +/- 4.6% versus 43.7% +/- 3.5%, p < 0.05), whereas hemodynamic variables failed to distinguish these groups. In those patients requiring inotropes, there was a significant negative correlation of fractional shortening with the peak dose (r = -0.87, p < 0.01) and the duration of inotropic support (r = -0.62, p < 0.05). The total ischemic time of the allograft (206 +/- 22 minutes, range 77 to 359) did not correlate with the subsequent fractional shortening, but patients requiring inotrope support after the operation had significantly longer ischemic times (259 +/- 22 versus 138 +/- 22 minutes, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗