Biomedical subjects

A L Mark

Publications and source records attributed to A L Mark.

At least 37 records · Page 2Linked to original sources

PubMed1997

Familial hypomagnesemia maps to chromosome 9q, not to the X chromosome: genetic linkage mapping and analysis of a balanced translocation breakpoint.

Familial hypomagnesemia with secondary hypocalcemia (HSH) (MIM 307600) was studied in three inbred Bedouin kindreds from Israel. The three kindreds, one extended and two nuclear families, contained 13 affected individuals, 11 males and two females. Assuming that the individuals affected with hypomagnesemia shared a chromosomal region inherited from a common ancestor, we used a DNA pooling strategy in a genome-wide search for loci which show homozygosity for shared alleles in affected individuals. DNA samples from affected individuals within a single kindred were pooled and used as the template for PCR amplification of short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected siblings and parents were used as controls. A shift towards homozygosity was observed in the affected DNA pool compared with the control pools with D9S301 (GATA7D12). Genotyping of individual DNA samples with D9S301 and several flanking markers confirmed linkage to chromosome 9 with maximum LOD scores of 3.4 (theta = 0.05), 3.7 (theta = 0) and 2.3 (theta = 0) for the three families. We have identified a 14 cM interval on chromosome 9 (9q12-9q22.2), flanked by proximal marker D9S1874 and distal marker D9S1807, within which all affected individuals from the three kindreds are homozygous for a shared haplotype. The disease segregates with a common affected haplotype in the three families, suggesting that hypomagnesemia is caused by a common ancestral mutation in these families. Although HSH has been previously reported to be X linked, these linkage data demonstrate that the disorder is an autosomal recessive disease in these kindreds. Mapping of a chromosomal breakpoint in a somatic cell line established from a patient with HSH and a balanced X;9 translocation placed the chromosomal breakpoint in a 500 kb region flanked by D9S1844 and D9S273. Identification of the gene responsible for hypomagnesemia will provide insight into the regulation of this essential cation.

Arabs↗

PubMed1997

Contrasting autonomic and hemodynamic effects of insulin in healthy elderly versus young subjects.

Acute increases in plasma insulin produce both sympathoexcitation and vasodilation in normal young adults. Aging is associated with insulin resistance and may alter the sympathetic or the vascular responses to insulin. Therefore, we assessed sympathetic and vascular responses to acute physiological increases in plasma insulin levels in 10 healthy, normotensive elderly (65+/-2 years) and 12 normal young (27+/-1 years) subjects matched for body mass index (25+/-1 kg/m2 in both groups). We measured muscle sympathetic nerve activity (microneurography), FBF (plethysmography), heart rate, and blood pressure and calculated forearm vascular resistance and insulin sensitivity (M value) during a 90-minute hyperinsulinemic/euglycemic clamp. M values were 4.3+/-0.4 mg x kg(-1) x min(-1) in the elderly and 8.4+/-1.4 mg x kg(-1) x min(-1) in the young subjects (P<.05). Baseline muscle sympathetic nerve activity was higher in the elderly subjects (33+/-3 versus 15+/-2 bursts per minute, P<.05); however, the absolute and percent increases in muscle sympathetic nerve activity were smaller in the elderly than in the young subjects (+10+/-1 versus +15+/-1 bursts per minute, or +37+/-11% versus +110+/-16%, P<.05). Forearm vascular resistance decreased with insulin from 46+/-2 to 31+/-3 units in the young but increased with insulin in the elderly subjects from 37+/-3 to 47+/-7 units (P<.05). Heart rate increased in young but not in elderly subjects. Insulin did not change blood pressure in either group. In conclusion, as opposed to vasodilation in young adults, insulin caused vasoconstriction in healthy elderly individuals. The failure of the vasodilator action of insulin in the elderly may permit even modest insulin-induced sympathoexcitation to elicit vasoconstriction. We speculate that the vasoconstrictor response to insulin may further potentiate insulin resistance in the elderly.

Adult↗

PubMed1997

Effects of alcohol on sympathetic activity, hemodynamics, and chemoreflex sensitivity.

Alcohol intake has been shown to worsen obstructive sleep apnea and increase nocturnal hypoxemia. The mechanisms of this action are unclear. Animal studies suggest that a reduction in chemoreflex sensitivity may be implicated. Using a double-blind, randomized, vehicle-controlled design, we tested the hypothesis that oral alcohol intake depresses chemoreflex sensitivity in humans. We examined the effects of oral alcohol intake (1.0 g/kg body wt) on blood pressure, heart rate, heart rate variability, muscle sympathetic nerve activity, forearm vascular resistance, and minute ventilation in 16 normal male subjects. Peripheral and central chemoreflex sensitivity were measured in response to hypoxia (n = 10) and hypercapnia (n = 6), respectively. Plasma alcohol increased from 0 to 23.2 +/- 1.5 mmol/L (107 +/- 7 mg/dL) at 60 minutes and 20.2 +/- 1 mmol/L (93 +/- 4 mg/dL) at 85 minutes after alcohol intake (P < .0001). Alcohol induced an increase in heart rate from 59 +/- 2 to 66 +/- 2 beats per minute (P < .01) and increased the ratio of low- to high-frequency variability of heart rate (P < .05). Although alcohol increased sympathetic nerve activity by up to 239 +/- 22% of baseline values (P < .01), forearm vascular resistance after alcohol was lower than that after vehicle (P < .05). Blood pressure did not increase compared with the vehicle session. Oxygen saturation during hypoxia after alcohol was 4 +/- 1% lower than it was during hypoxia after vehicle (P < .05) although arterial blood PO2 was unchanged. Alcohol did not affect the cardiovascular, sympathetic, or ventilatory responses to either hypoxia or hypercapnia. Acute increases in plasma alcohol increase heart rate and sympathetic nerve activity; blood pressure is not increased, probably because of vasodilator effects of alcohol. Alcohol does not alter chemoreflex responses to hypoxia or hypercapnia; thus, alterations in chemoreflex sensitivity are unlikely to explain the effects of alcohol on sleep apnea. Alcohol may reduce the affinity of hemoglobin for oxygen.

Adult↗

PubMed1997

Sympathetic and cardiorenal actions of leptin.

Body weight is tightly regulated physiologically. The recent discovery of the peptide hormone leptin has permitted more detailed evaluation of the mechanisms responsible for control of body fat. Leptin is almost exclusively produced by adipose tissue and acts in the CNS through a specific receptor and multiple neuropeptide pathways to decrease appetite and increase energy expenditure. Leptin thus functions as the afferent component of a negative feedback mechanism to control adipose tissue mass. Increasing evidence suggests that leptin may have wider actions influencing autonomic, cardiovascular, and endocrine function. Intravenous leptin increases norepinephrine turnover and sympathetic nerve activity to thermogenic brown adipose tissue. Studies from our laboratory suggest that leptin also increases sympathetic nerve activity to kidney, hindlimb, and adrenal gland. However, systemic administration of leptin does not acutely increase arterial pressure or heart rate in anesthetized animals. Thus, longer-term exposure to hyperleptinemia may be necessary for full expression of the expected pressor effect of renal sympathoexcitation. Alternatively, leptin may have additional cardiovascular actions to oppose sympathetically mediated vasoconstriction. Leptin in high doses increases renal sodium and water excretion, apparently through a direct tubular action. In addition, leptin appears to increase systemic insulin sensitivity, even in the absence of weight loss. Although we are at an early stage of understanding, we speculate that abnormalities in the actions of leptin may have implications for the sympathetic, cardiovascular, and renal changes associated with obesity.

Adipose Tissue↗

PubMed1996

Tonic chemoreflex activation does not contribute to elevated muscle sympathetic nerve activity in heart failure.

BACKGROUND: Sympathetic activation in heart failure may be due to an increase in sympathetic excitatory influences or to a decrease in inhibitory signals to the brain stem. Chemoreflex sensitivity may be increased in patients with heart failure. The present study tested the hypothesis that tonic activation of excitatory chemoreceptor afferents contributes to the elevated sympathetic activity in heart failure. METHODS AND RESULTS: We recorded sympathetic nerve activity to muscle circulation from the peroneal nerve of 12 chronic heart failure patients while the patients were breathing room air and during deactivation of the chemoreceptors while the patients were breathing a 100% O2 gas mixture. All patients except 2 were in class III of the New York Heart Association functional classification. Left ventricular ejection fraction defined by radionuclide ventriculography was 24 +/- 2% (mean +/- SE). We also obtained measurements of resting sympathetic nerve activity in 9 healthy control subjects to document that sympathetic nerve activity was elevated in heart failure subjects. Resting sympathetic nerve activity was 59 +/- 5 bursts/min in heart failure patients versus 36 +/- 4 bursts/min in control subjects (P < .01). In heart failure patients, oxygen administration increased oxygen saturation from 94 +/- 0.9% to 99 +/- 0.3% (P < .0001). This increase in oxygen saturation did not affect resting muscle sympathetic nerve activity (798 +/- 122 U/min while patients breathed room air and 824 +/- 35 U/min during 100% O2 breathing) or blood pressure. CONCLUSIONS: Increased efferent sympathetic activity to muscle circulation in patients with heart failure is not explained by tonic activation of excitatory chemoreflex afferents.

Aged↗

PubMed1996

Effect of the stress level achieved during symptom-limited exercise technetium-99m sestamibi myocardial tomography on the detection of coronary artery disease.

BACKGROUND: The stress level achieved during exercise thallium 201 myocardial imaging may influence its sensitivity for detecting coronary artery disease (CAD). The effect of exercise adequacy on the accuracy of technetium-99m sestamibi (MIBI) imaging has not been studied. HYPOTHESIS: The study was undertaken to assess the effect of exercise level achieved on sensitivity for detecting CAD. METHODS: A consecutive series of 250 patients (mean age 60 +/- 10 years) with CAD by angiography underwent symptom-limited exercise MIBI single-photon emission computed tomography. Single-vessel CAD was found in 66 patients, double-vessel CAD in 84, triple-vessel CAD in 80, and left main disease in 20. RESULTS: No significant differences were found in sensitivities of an abnormal MIBI scan or a reversible defect among 102 patients reaching 85% of age-predicted heart rate and 148 who did not (82 vs. 89% and 66 vs. 70%, respectively, p = NS). Patients (n = 128) able to exercise < or = 6 min had a higher incidence of abnormal scans and reversible defects than 122 patients with a greater exercise duration (91 vs. 82% and 75 vs. 61%, respectively, both p < 0.05). Sensitivity of an abnormal MIBI scan for multivessel disease was greater than for single-vessel disease in patients who achieved > or = 85% of age-predicted heart rate (91 vs. 59%, p < 0.01) and in those who exercised > 6 min (89 vs. 66%, p < 0.01). No significant differences in the sensitivities of an abnormal MIBI study for multivessel versus single-vessel CAD were seen in patients achieving lower peak levels of exercise. Sensitivity of ischemic ST depression was lower than that of MIBI tomography at all levels of exercise. CONCLUSIONS: The sensitivity of exercise MIBI tomography for angiographic CAD is relatively independent of the peak heart rate achieved. Exercise duration of > 6 min is associated with a significantly higher MIBI abnormality rate than a duration of > 6 min, possibly reflecting the effect of myocardial ischemic burden on exercise ventricular function. Regardless of level of stress or its duration, exercise MIBI tomography improves the sensitivity for CAD detection compared with stress-induced ischemic ST depression.

Adult↗

PubMed1996

Dipyridamole technetium 99m sestamibi myocardial tomography for preoperative cardiac risk stratification before major or minor nonvascular surgery.

The value of dipyridamole technetium 99m sestamibi (MIBI) tomography for preoperative cardiac risk stratification was assessed in 285 consecutive patients being considered for nonvascular surgery. A "major" (n = 140) or "minor" (n = 89) nonvascular procedure was later done in 229 of these patients < or = 4 months after dipyridamole testing. Perioperative cardiac events (unstable angina, acute ischemic pulmonary edema, nonfatal myocardial infarction, or cardiac death) occurred in 11 (8%) patients undergoing major nonvascular surgery and 1 (1%) undergoing a minor procedure. The only clinical or scintigraphic variables associated with significantly increased perioperative cardiac risk in patients having major surgery were Goldman class > or = II, an abnormal MIBI scan, and a fixed perfusion defect. In these patients, cardiac events occurred in 1% of those who had a normal MIBI study, 14% of those with an abnormal scan (p < 0.01), 12% with a reversible MIBI defect (p = 0.29), and 17% with a fixed MIBI defect (p < 0.01). In the 60 patients whose Goldman class was > or = II, only an abnormal MIBI study and a fixed perfusion defect were associated with incremental risk of a perioperative cardiac event. The incidence of perioperative cardiac events in these patients was 4% with a normal MIBI scan, 27% with an abnormal study (p < 0.05), 24% with a reversible MIBI defect (p = 0.45), and 37% with a fixed defect (p < 0.01). Event rates were low in patients having minor nonvascular surgery; none of the 25 with a normal MIBI study and only 1 of the 64 with an abnormal scan had a perioperative cardiac event (p = not significant (NS). We conclude that dipyridamole MIBI tomography can provide important prognostic information in patients having major nonvascular surgery. A normal MIBI study indicates a low risk of perioperative cardiac events, whereas an abnormal study in patients with Goldman class > or = II undergoing major surgery is associated with significantly increased risk. The prognostic value of MIBI tomography in patients at low clinical risk undergoing minor surgery is limited.

Aged↗

PubMed1996

Genetic characterization of the "new" Harlan Sprague Dawley Dahl salt-sensitive rats.

In 1994, it was reported that Dahl salt-sensitive SS/Jr rats supplied by Harlan Sprague Dawley were genetically contaminated and resistant to the pressor effects of a high salt diet. Harlan Sprague Dawley subsequently developed new pedigree expansion and production colonies from their foundation colony to supply new, purportedly inbred, Harlan Sprague Dawley SS/Jr (S(HSD)). To evaluate the genetic integrity and salt sensitivity of thse new S(HSD), we performed genotyping (microsatellite DNA markers) and phenotyping (radiotelemetric arterial pressure) of 12 S(HSD), 16 "authentic" SS/Jr from the inbred colony of John Rapp (S(Rapp)), 9 Harlan Sprague Dawley salt-resistant SR/Jr (R(HSD)), and (genotyping only) 6 known "contaminated" Harlan Sprague Dawley Dahl SS/Jr (S*). In the genotyping studies, 20 of 22 markers revealed polymorphisms between S(Rapp) and S* and 18 were polymorphic between S(Rapp) and R(Rapp), but none of the 22 markers revealed polymorphisms between S(Rapp) and the new S(HSD). The phenotyping studies showed that during an ultra-low salt diet, mean arterial pressure was higher (P < .05) in both authentic S(Rapp) (129 +/- 2 mm Hg; mean +/- SE) and new S(HSD) (120 +/- 2 mm Hg) than in R(HSD) (93 +/- 1 mm Hg). A high salt diet increased mean arterial pressure in every S(HSD) and S(Rapp). Increases in mean arterial pressure after 4 weeks of a high salt diet were significantly (P < 0.05) greater in authentic S(Rapp) (+51 +/- 3 mm Hg) than in new S(HSD) (+39 +/- 3 mm Hg). In addition, salt-induced mortality was significantly greater in S(Rapp) (62.5%) than S(HSD) (8.3%) after 8 weeks (P < 0.01). S(HSD) were genotypically indistinguishable from S(Rapp), had an elevated arterial pressure on a low salt diet, and had a pressor response to salt. Thus, the new S(HSD) supplied to us had several characteristics of inbred Dahl SS/Jr and did not have evidence of the previously detected genetic contamination. However, phenotypic characteristics such as body weight, salt-induced hypertension, and mortality were significantly different in S(HSD) compared with S(Rapp). This may reflect genetic differences between these two strains or differences in environmental factors and suggests that the S(HSD) and S(Rapp) may now constitute distinct substrains of Dahl SS/Jr.

Animals↗

PubMed1996

The sympathetic nervous system in hypertension: a potential long-term regulator of arterial pressure.

UNLABELLED: INCREASED SYMPATHETIC NERVE ACTIVITY IN HYPERTENSION: Two techniques (the microneurographic method for intraneural recordings of sympathetic nerve activity and radiotracer techniques for study of norepinephrine kinetics) have been used recently to obtain sophisticated insight into regional sympathetic function in humans. Persuasive evidence now indicates that young mildly hypertensive humans have increased sympathetic neural activity. LONG-TERM REGULATION OF ARTERIAL PRESSURE: Three credible mechanisms have been proposed to sustain long-term sympathetic nervous influences in hypertension: antinatriuretic and renin stimulating effects of the renal sympathetic nerves, sympathetic influences on the development of vascular membrane properties and trophic effects of the sympathetic nerves on vascular and cardiac muscle. CONCLUSION: There is increasing evidence that the sympathetic nervous system may play a primary role in the pathogenesis of essential hypertension and the long-term regulation of arterial pressure.

Animals↗

PubMed1995

Sympathetic dysregulation in heart failure: mechanisms and therapy.

Heart failure is accompanied by sympathetic over-activity, which contributes to the pathophysiology and to poor prognosis. This paper reviews the mechanisms and potential therapy for sympathetic dysregulation in heart failure (HF). Several points are emphasized: (1) There is increased sympathetic activity to skeletal muscle, kidney, and heart, but not to skin, in HF. This information challenges the concept of generalized sympathetic activation in HF and suggests that the factors responsible for sympathetic activation result in a partitioning of excess sympathetic outflow to some but not all tissues and organs. (2) The sympathetic dysregulation appears to result from impairment in cardiac and arterial baroreceptor restraint on sympathetic activity, but this abnormality in baroreceptor function may result from abnormal humoral and/or ionic influences acting on baroreceptor endings or in the central nervous system and not from intrinsic structural abnormalities in baroreceptors. This distinction has potential therapeutic importance because abnormalities in humoral or ionic mechanisms would more likely lend themselves to therapeutic modulation. (3) Digitalis sensitizes cardiac and arterial baroreceptors and inhibits sympathetic nerve activity in patients with HF. This sympathoinhibitory influence of digitalis is maintained during chronic therapy. These observations support the concept that the therapeutic effects of digitalis include autonomic modulation in addition to positive inotropism. In a broader concept, these observations suggest that sympathetic modulation may represent an important target for drugs for treatment of heart failure.

Blood Vessels↗

PubMed1995

Influence of resting sympathetic activity on reflex sympathetic responses in normal man.

Reflex sympathetic responses to physiologic stress are known to be modulated by afferent sensory mechanisms. However, the potential influence of baseline sympathetic tone on these reflex-mediated responses is unclear. To test the hypothesis that the resting level of muscle sympathetic nerve activity (MSNA) influences reflex-mediated changes in MSNA in normal man, MSNA, blood pressure (BP), central venous pressure (CVP), and heart rate (HR) was measured in 38 normal subjects at rest and during deactivation of cardiopulmonary baroreceptors (CPBR) with lower body negative pressure (LBNP; 0 to -15 mmHg). A cold pressor test (CPT) also was performed in 25 subjects. Incremental LBNP decreased CVP (from 5.8 +/- 0.4 to 2.1 +/- 0.4 mmHg) without altering BP or HR, and increased in MSNA burst frequency (from 22.5 +/- 1.4 to 30.2 +/- 1.4 bursts/min). There was no significant correlation between levels of MSNA and any haemodynamic parameter at rest. There was a significant inverse correlation between CPBR sympathetic gain (CPBRSG, slope of the regression line correlating percentage change in MSNA (bursts/min) per mmHg decrease in CVP during non-hypotensive LBNP) and resting MSNA (r = -0.72, p < 0.0001). A significant inverse correlation was also observed between MSNA responses to the CPT (expressed as percentage change in burst frequency from control) and the resting MSNA (r = -0.63, p = 0.008). Sixteen subjects were restudied 3 weeks to 14 months later to determine reproducibility of measurements; resting BP and CVP, HR, and MSNA levels were not different between the two sessions, as was CPBRSG. In ten of these 16 subjects, in whom the CPT was repeated the MSNA response also was not significantly different. These studies demonstrate an inverse relationship between resting MSNA and both cardiopulmonary baroreflex sensitivity and sympathetic neural responses to the non-baroreflex mediated cold pressor stimulus. These findings suggest that resting levels of sympathetic neural activity influence reflex-mediated changes in muscle sympathetic nerve activity.

Adult↗

PubMed1995

Dissociation of sympathoexcitatory and vasodilator actions of modestly elevated plasma insulin levels.

OBJECTIVE: To determine sympathetic and vascular responses to modest increases in plasma insulin level. BACKGROUND: Most studies of sympathetic and vascular actions of insulin have evaluated high plasma insulin levels ( > 50 microU/ml). Those levels increase sympathetic nerve activity but also cause vasodilation. Hypertension and obesity are associated with only modestly elevated fasting insulin levels. METHODS: We investigated the effects of a 90 min low-dose hyperinsulinemic euglycemic clamp on muscle sympathetic nerve activity (microneurography), forearm vascular resistance (plethysmography), heart rate, blood pressure and central venous pressure. Insulin and vehicle sessions were performed in 12 normal subjects. RESULTS: Plasma insulin levels were elevated from values of 10 +/- 2 in the fasting state to 25 +/- 3 microU/ml during insulin infusion. Insulin levels did not change during vehicle administration. Muscle sympathetic nerve activity increased from 16 +/- 2 to 25 +/- 3 burst/min during the insulin session and did not change during vehicle administration. In contrast to muscle sympathetic nerve activity, forearm vascular resistance did not change during insulin administration (from 50 +/- 3 to 51 +/- 4 U). Forearm vascular resistance tended to fall during vehicle administration (from 45 +/- 2 to 37 +/- 3 U). There were no changes in heart rate, blood pressure and central venous pressure that could be attributed to insulin. CONCLUSIONS: Modest elevations of plasma insulin levels produce sympathetic activation similar to that caused by high levels, but, in contrast to high levels modest elevations in plasma insulin level do not decrease forearm vascular resistance. The present findings suggest a dissociation between sympathoexcitatory and vascular actions of insulin at low plasma levels.

Adult↗

PubMed1995

Renal sympathetic nerve activity is increased in obese Zucker rats.

A low level of sympathetic nerve activity (SNA) to brown adipose tissue has been found in genetically obese Zucker rats and may promote obesity through decreased thermogenesis. In contrast, acquired obesity is reportedly associated with increased SNA. To determine whether low SNA levels in obese Zucker rats extend to the kidney, we compared baseline levels of renal SNA in obese and lean conscious unrestrained Zucker rats fed for 2 weeks on low salt (0.4% NaCl) and high salt (8.0% NaCl) diets. Baseline renal SNA was calculated from multifiber recordings obtained before death under conscious, resting conditions and after death. Body weight averaged 490 +/- 12 g (mean +/- SEM) in obese rats (n = 17) and 339 +/- 7 g in lean rats (n = 19). Mean arterial pressure did not differ in obese and lean Zucker rats fed the low salt diet. However, on the high salt diet, mean arterial pressure was significantly higher in obese rats (n = 8) than in lean rats (n = 9) (113 +/- 3 and 101 +/- 3 mm Hg, respectively; P < .05). Baseline renal SNA was approximately 2 to 2.5 times higher (P < .05) in obese rats than in lean rats in all groups. These studies suggest that obese Zucker rats have heightened levels of SNA to the kidney in contrast to reduced SNA to brown adipose tissue.

Animals↗

PubMed1995

Genetic factors determine the blood pressure response to insulin resistance and hyperinsulinemia: a call to refocus the insulin hypothesis of hypertension.

We have briefly reviewed the controversy regarding the role of insulin resistance and hyperinsulinemia in the pathogenesis of hypertension in an attempt to emphasize the evidence in support of this concept. In so doing, we have highlighted the concept that genetic factors may determine sensitivity or resistance to the hypertensive effects of insulin resistance and hyperinsulinemia. We hope that this idea will help to reconcile seemingly conflicting evidence on this hypothesis and will focus future research.

Animals↗

PubMed1995

Sympathetic nerve activity to nonactive muscle of the exercising and nonexercising limb.

The purpose of this study was to determine whether efferent sympathetic nerve activity is different to resting skeletal muscles from the exercising and nonexercising limb. MSNA was measured by microneurography in both legs (peroneal nerve) in six subjects during 2 min of unilateral isometric knee extension (IKE; 10-30% of maximum voluntary contraction (MVC)) followed by postexercise circulatory occlusion (PECO). Additional studies using isometric handgrip (30% MVC) followed by PECO were performed. IKE produced significant increases in mean arterial pressure (15 +/- 2 mm Hg) and heart rate (10 +/- 2 bpm). During PECO, mean arterial pressure remained significantly elevated (6 +/- 1 mm Hg) whereas heart rate returned to control. MSNA (bursts.min-1) was not different between the two limbs during control, IKE, PECO, and recovery. Seventy-five to eighty percent of all sympathetic nerve discharges occurred simultaneously in both legs, with the remaining percentage of sympathetic nerve discharges being divided almost equally between the nonexercising and exercising leg. Isometric handgrip produced significant increases in MSNA to the two resting legs with the percent of sympathetic discharges to the two legs being similar to that during IKE. These results indicate that MSNA is similar to the resting muscle in the exercising and nonexercising leg during brief, submaximal isometric exercise (< or = 30% MVC) and postexercise muscle ischemia.

Adult↗

PubMed1994

Modulation of sympathetic nerve activity during posthandgrip muscle ischemia in humans.

To evaluate modulation of muscle sympathetic nerve activity (MSNA) during posthandgrip muscle ischemia (PHGMI), subjects performed 2 min of isometric handgrip at 33% of maximal voluntary contraction (MVC) followed by 2 min of PHGMI produced by forearm vascular occlusion. The response to PHGMI was studied in the absence and again during the addition of contralateral rhythmic handgrip (RHG; 40 times/min) at 15% (n = 6) and 30% (n = 10) MVC during the second minute of the PHGMI. Additionally, to isolate the effect of central command, response to PHGMI was studied during attempted RHG after sensory nerve blockade (n = 5). RHG for 2 min at 15 and 30% MVC and attempted RHG for 2 min did not increase MSNA. Isometric handgrip elicited an 130 +/- 48% increase in MSNA (P < 0.05), which was maintained during PHGMI. RHG at 15 and 30% MVC elicited an attenuation of MSNA (-10 +/- 7% and -14 +/- 6%, respectively) when performed during the second minute of PHGMI (P < 0.05). In contrast, attempted RHG did not significantly affect MSNA during PHGMI. The findings demonstrate modulation of MSNA during activation of the muscle metaboreflex. The attenuation of metaboreceptor-mediated increases in MSNA appear to be the result of mechanosensitive muscle afferents and not central command.

Adult↗

PubMed1994

Intracerebroventricular insulin produces nonuniform regional increases in sympathetic nerve activity.

Insulin has been shown to increase sympathetic nerve activity (SNA). Although it has been proposed that insulin acts within the central nervous system (CNS) to increase sympathetic neural outflow, there is little evidence for direct central neural sympathoexcitatory effects of insulin. To determine whether intracerebroventricular insulin elicits increases in peripheral SNA, we infused insulin (0.1 microU/min, low; 10 microU/min, medium; and 100 microU/min, high doses) or artificial cerebrospinal fluid (aCSF) into the third cerebral ventricle of chloralose-anesthetized Wistar rats while recording lumbar SNA. In separate animals, 10 microU/min of insulin were infused while recording adrenal SNA and renal SNA. Blood glucose and plasma insulin levels did not significantly change during intracerebroventricular infusion of insulin. Lumbar SNA, expressed as percentage of baseline, did not change in rats infused with aCSF (+ 13% +/- 8%) but increased significantly in rats infused with low (+ 72 +/- 17%), medium (+ 119 +/- 30%), and high (+ 113 +/- 25%) doses of insulin (P < 0.05). Intracerebroventricular insulin failed to significantly increase adrenal SNA or renal SNA. Blood pressure and heart rate did not change during insulin infusion. The results indicate that administration of insulin into the third cerebral ventricle produces regionally nonuniform increases in sympathetic neural outflow in the absence of changes in blood glucose or plasma insulin.

Adrenal Glands↗

PubMed1994

Independent control of skin and muscle sympathetic nerve activity in patients with heart failure.

BACKGROUND: Sympathetic excitation characterizes heart failure, but the underlying mechanisms remain unknown. Abnormal baroreflex restraint of sympathetic neural outflow has been proposed, since baroreflexes are known to be abnormal in heart failure. The purpose of this study was to determine if sympathetic activation in humans with heart failure is limited to regions governed by the baroreflexes or is generalized to other regions free from baroreflex control. METHODS AND RESULTS: We report the first direct recordings of skin sympathetic nerve activity (free from baroreflex control) in humans with heart failure and compare simultaneous skin and muscle (baroreflex-dependent) sympathetic peroneal nerve activity in six patients with severe heart failure (mean left ventricular ejection fraction, 0.19 +/- 0.06) and in six age-matched normal control subjects. Although muscle sympathetic nerve activity was markedly increased in heart failure patients (heart failure versus controls, 69 +/- 3 versus 21 +/- 2 bursts per minute; P < .001), skin sympathetic nerve activity was not increased (heart failure versus controls, 12 +/- 1 versus 15 +/- 1 bursts per minute; P = NS). CONCLUSIONS: The finding that skin sympathetic nerve activity in contrast to muscle sympathetic nerve activity is not increased in heart failure supports the concept that an altered reflex system, such as the baroreflexes, with nonuniform effects on muscle and skin sympathetic nerve activity, underlies sympatho-excitation in heart failure.

Adult↗