Search PubMed⌕ Search

Biomedical subjects

A L Mark

Publications and source records attributed to A L Mark.

At least 145 records · Page 8Linked to original sources
PubMed1983

Effects of propranolol on reflex vascular responses to orthostatic stress in humans. Role of ventricular baroreceptors.

To evaluate the role of ventricular baroreceptors in humans, we studied the effects of propranolol on reflex vasoconstrictor responses to simulated orthostatic stress. We measured forearm vascular resistance in 10 normal males in the control state and during lower body negative pressure (LBNP) at -10 and -40 mm Hg before and after propranolol (0.1 mg/kg i.v.). Baseline forearm vascular resistance showed no significant change: 23.9 +/- 3.4 U (+/- SEM) before vs 28.0 +/- 0.5 U after propranolol. Reflex increases in forearm vascular resistance during LBNP at -10 and -40 mm Hg were 5.2 +/- 1.2 and 21.2 +/- 6.6 U before and 3.4 +/- 1.2 and 10.6 +/- 2.2 U, respectively, after propranolol. Thus, propranolol significantly (p less than 0.05) reduced responses to LBNP at -40 mm Hg. In contrast to the effects with LBNP, propranolol did not attenuate increases in forearm vascular resistance during the cold pressor test and handgrip, thus excluding a nonspecific depression of reflexes. We also studied the effects of propranolol on carotid baroreflex-mediated vasoconstrictor responses to neck pressure at 15 and 30 mm Hg. Propranolol had no significant effect on the vasoconstrictor responses to neck pressure. In conclusion, propranolol selectively attenuates vasoconstrictor responses to LBNP. We suggest that this results from a propranolol-induced decrease in the activity of cardiac ventricular baroreceptors. The results support the view that ventricular baroreceptors play an important role in reflex adjustments to orthostatic stress in humans.

Adult↗
PubMed1983

Inhibition of cardiac sympathetic nerve activity during intravenous administration of lidocaine.

The antiarrhythmic action of lidocaine has been attributed solely to its direct electrophysiological effects on the heart. However, lidocaine is particularly effective in treating ventricular arrhythmias associated with increased sympathetic activity, e.g., in myocardial infarction and digitalis toxicity. We tested the hypothesis that lidocaine administered intravenously depressed cardiac sympathetic nerve activity (CSNA). We measured CSNA in six dogs in control state and after lidocaine in doses of 0.625, 1.25, and 2.5 mg/kg i.v. over 2 min. These doses of lidocaine produced graded decreases of CSNA of -8 +/- 2, -18 +/- 1, and -41 +/- 5%, respectively (P less than 0.05, mean +/- SE). In six additional experiments the bolus of lidocaine was followed by an infusion for 20 min (1.25 mg/kg followed by 100 micrograms/kg per min and 2.5 mg/kg followed by 200 micrograms/kg per min). Infusion of lidocaine maintained depression of CSNA at a level that was 23 +/- 3 and 35 +/- 5% less than control (P less than 0.05), respectively, at plasma lidocaine levels of 5.2 +/- 0.6 and 7.5 +/- 1.4 micrograms/ml, respectively. CSNA returned to control during recovery periods. CSNA did not decrease with the passage of time or administration of vehicle. In five dogs with vagi intact, carotid sinuses isolated and held at a pressure of 100 mmHg, and aortic baroreceptors denervated, administration of lidocaine (2.5 mg/kg followed by 200 micrograms/kg per min) decreased renal nerve activity to 71 +/- 8% of control. Increases in left ventricular systolic pressure and maximum derivative of pressure with respect to time (dP/dtmax) resulting from electrical stimulation of preganglionic sympathetic nerves were not significantly altered by lidocaine, but were markedly attenuated by hexamethonium, a ganglionic blocker. In conclusion, lidocaine administered intravenously produces dose-dependent and sustained decreases in cardiac sympathetic nerve activity. These decreases can occur with therapeutic plasma levels. We speculate that this effect is due to central nervous system effects of the drug and that this effect may contribute to the antiarrhythmic actions of lidocaine.

Animals↗
PubMed1982

Normal exercise capacity in patients with severe left ventricular dysfunction: compensatory mechanisms.

About one-third of patients who have severe left ventricular dysfunction can achieve normal levels of exercise. To elucidate the mechanisms that permit this to occur, we studied six patients with severe left ventricular dysfunction (average left ventricular ejection fraction 17 +/- 2.5% [mean +/- SEM]) who achieved nearly normal levels of exercise tolerance (greater than 11 minutes of treadmill exercise, Sheffield protocol). All patients had normal pulmonary function at rest and during exercise. Hemodynamics were measured at rest and during supine and upright exercise. The major mechanisms of the preserved exercise capacity in these patients were chronotropic competence, ability to tolerate elevated wedge pressures (33 +/- 3 mm Hg) without dyspnea, ventricular dilation, and increased levels of plasma norepinephrine at rest and during exercise. Also, whereas peripheral vascular resistance was unchanged during supine exercise, it decreased by 50% during similar levels of upright exercise. As a consequence, increases in cardiac output from rest to exercise were greater during upright than supine exercise (100% vs 50%, respectively) (p less than 0.05), and pulmonary wedge pressures were lower during upright than supine exercise (21 +/- 5 mm Hg vs 33 +/- 3 mm Hg). Thus, multiple mechanisms permit some patients with severe left ventricular dysfunction to achieve normal levels of exercise. These studies emphasize that left ventricular function must be assessed by direct means rather than inferring function of the left ventricle from the results of an exercise tolerance test.

Aged↗
PubMed1982

Forearm vascular resistance in the upper and lower quintiles of blood pressure in adolescent boys: The Muscatine Study.

Nineteen 16 year old white boys whose systolic blood pressures were in the upper (r = 9) and lowest (r = 10) quintile of the distribution in two school surveys in 1975 and 1977 were selected. In 1979 forearm blood flow, blood pressure and heart rate were measured at rest, and during peak reactive hyperemia. Minimal forearm vascular resistance during peak reactive hyperemia was used to assess the structural contribution to vascular resistance. At rest the high quintile group again had significantly higher blood pressures than the low quintile group but their forearm vascular resistance was not significantly different. The high quintile group showed significantly higher minimal forearm vascular resistance at peak reactive hyperemia. The latter observation suggests that there is a difference in the structural contribution to forearm vascular resistance in adolescents with blood pressure in the upper versus lower quintile of the distribution.

Adolescent↗
PubMed1982

Central mechanisms in DOC-salt hypertensive rats.

These experiments were intended to elucidate the role of central mechanisms in the maintenance of high blood pressure produced by deoxycorticosterone (DOC) and salt in rats. We investigated the central effect of angiotensin (AII) on systemic arterial blood pressure and plasma arginine vasopressin (AVP) in DOC-salt and control rats. There was a pronounced augmentation of the pressor responsiveness to centrally injected AII in DOC-salt hypertensive rats; but there was no difference in AII induced AVP release in DOC-salt hypertensive rats compared to sham controls. The increase in vascular resistance of the perfused hindquarters induced by stimulation of the lumbar sympathetic chains did not change in DOC-salt hypertensive rats although the increases induced by norepinephrine (NE) were potentiated at the higher doses. Pressor responsiveness of the DOC-salt hypertensive rats to i.v. administration of AII, AVP and NE was shown to be augmented by factors of 3.6, 2.5 and 1.8 respectively in DOC-salt rats. Reflex bradycardia to these pressor responses was attenuated indicating impairment of baroreflex function. The potentiation of pressor responses to centrally injected AII in DOC-salt hypertensive rats was greater than could be explained by augmented pressor responsiveness to iv NE and AVP. Neither baroreflex dysfunction, facilitated release of NE at sympathetic terminals, nor augmented release of AVP into the circulation could explain the potentiation. Therefore, our data suggested that selective central amplification of sympathetic vasomotor responses to centrally injected AII stimuli may play a role in the hypertension after 3 weeks of DOC-salt treatment in rats.

Angiotensin II↗
PubMed1980

Interaction of cardiopulmonary and somatic reflexes in humans.

Activation of cardiopulmonary receptors with vagal afferents results predominantly in reflex inhibition of efferent sympathetic activity, whereas activation of somatic receptors reflexly increases sympathetic activity to the heart and circulation. Previous studies in experimental animals indicate that there is an important interaction between these excitatory and inhibitory reflexes in the control of the renal circulation. The purpose of this study was to determine whether there is a similar interaction between somatic and cardiopulmonary reflexes in humans. The activity of the cardiopulmonary receptors was altered (reduced) with lower body negative pressure (-5 mm Hg), which causes a decrease in cardiac filling pressure and a small reflex increase in forearm vascular resistance without accompanying changes in arterial pressure. Activation of somatic receptors by isometric handgrip for 2 min at 10 and 20% of maximum voluntary contraction resulted in reflex vasoconstriction in the nonexercising arm. Lower body negative pressure at -5 mm Hg produced a threefold augmentation in the forearm vasoconstrictor response to isometric handgrip in the nonexercising arm. This increase in resistance was significantly greater (P < 0.05) than the algebraic sum of the increases in resistance resulting from lower body suction alone plus isometric handgrip alone. Furthermore, it occurred despite a greater rise in arterial pressure, which would be expected to decrease forearm vascular resistance through activation of arterial baroreceptors and through passive dilatation of forearm vessels. Thus, removal of the inhibitory influence of cardiopulmonary receptors by pooling blood in the lower extremities enhances the somatic reflex. These data suggest an interaction between cardiopulmonary and somatic reflexes in the control of forearm vascular resistance in man.

Adult↗
PubMed1979

Carotid and cardiopulmonary baroreceptor control of splanchnic and forearm vascular resistance during venous pooling in man.

1. This study evaluated the contribution of carotid and cardiopulmonary baroreceptors to reflex splanchnic and forearm vascular adjustments during venous pooling in man. We compared (a) responses to lower body suction which produces venous pooling with (b) responses to lower body suction plus simultaneous application of neck suction. The rationale was that simultaneous application of neck suction, which stretches carotid baroreceptors, would minimize the contribution of carotid baroreceptors to circulatory adjustments produced by lower body suction.2. Lower body suction at 40 mmHg decreased central venous pressure and arterial pulse pressure and increased forearm vascular resistance (plethysmography), splanchnic vascular resistance (indocyanine green dye clearance), and heart rate. Simultaneous application of neck suction prevented the tachycardia and most of the splanchnic vasoconstriction during lower body suction, but did not significantly attenuate the forearm vasoconstriction.3. The major findings in this study are first, that the splanchnic vasoconstrictor response during venous pooling is mediated primarily through carotid baroreceptors, and secondly, that carotid and cardiopulmonary baroreceptors produce strikingly contrasting and non-uniform regional vascular responses during venous pooling. Cardiopulmonary baroreceptors exert the predominant influence on forearm vascular resistance, but appear to have only a minor influence on splanchnic vascular resistance. Carotid baroreceptors produce most of the splanchnic vasoconstriction during venous pooling. but have a minor role in the forearm vasoconstriction.

Abdomen↗
PubMed1979

Effect of central venous pressure on arterial baroreflex control of heart rate.

There is considerable evidence that the level of afferent cardiopulmonary receptor activity modulates sinus node responses to arterial baroreflex stimulation in experimental animals. We tested the hypothesis that this reflex interaction occurs also in man by measuring sinus node responses to arterial baroreceptor stimulation with phenylephrine injection or neck suction, before and during changes of central venous pressure provoked by lower body negative pressure or leg and lower trunk elevation. Variations of central venous pressure between 1.1 and 9.0 mmHg did not influence arterial baroreflex mediated bradycardia. Baroreflex sinus node responses were augmented by intravenous propranolol, but the level of responses after propranolol was comparable during the control state, lower body negative pressure, and leg and trunk elevation. Sinus node responses to very brief baroreceptor stimuli applied during the transitions of central venous pressure also were comparable in the three states. We conclude that physiological variations of central venous pressure do not influence sinus node responses to arterial baroreceptor stimulation in man.

Adult↗
PubMed1979

Prevention of salt-induced hypertension in the Dahl strain by 6-hydroxydopamine.

Salt-induced hypertension in Dahl's genetically hypertensive rat has been attributed to humoral or renal factors. However, a recent study from our laboratory suggested that neurogenic mechanisms contribute to salt-induced increased in hindquarters vascular resistance in Dahl salt-sensitive (S) rats. In the present study, we examined the hypothesis that "chemical sympathectomy" with 6-hydroxydopamine (6-OHDA) prevents salt-induced hypertension and increased vascular resistance in S rats. Hypertension did not develop during high-salt diet (8% NaCl) in S rats treated with 6-OHDA, (75--100 mg/kg ip), whereas in rats treated with vehicle, hypertension developed after 4 wk of high salt diet. Chow consumption, sodium excretion, and weight gain were not altered by 6-OHDA. Hindquarters vascular resistance and neurogenic vasoconstrictor tone were significantly lower in S rats treated with 6-OHDA than in S rats treated with vehicle. 6-OHDA also significantly reduced responses to direct sympathetic nerve stimulation and tyramine. These results suggest that an intact sympathetic nervous system plays an essential role in the development of salt-induced increase in blood pressure in Dahl S rats.

Animals↗
PubMed1978

Influence of low- and high-pressure baroreceptors on plasma renin activity in humans.

We evaluated effects of the low- and high-pressure baroreceptors on plasma renin activity (immunoassay) using graded lower body suction (LBS) in six healthy men. LBS at -10 and -20 mmHg for 10 min decreased central venous pressure without changing arterial pressure and thereby presumably reduced low- but not high-pressure baroreceptor inhibition of renin release. LBS at these levels produced forearm vasoconstriction, but did not increase renin. LBS at -40 mmHg decreased central venous and arterial pulse pressure and thus reduced both low- and high-pressure baroreceptor inhibition. LBS at this level produced forearm vasoconstriction and tachycardia and increased renin from 2.1 +/- 0.4 (mean +/- SE to 7.4 +/- 1.4 ng.ml-1.h-1 (P less than 0.05). In summary, reduction in low-pressure baroreceptor inhibition in humans did not increase renin in the presence of physiological tonic inhibition from high-pressure baroreceptors. Increases in renin did not occur until there was combined reduction of high- and low-pressure baroreceptor inhibition on plasma renin activity.

Adult↗
PubMed1978

Preferential distribution of inhbititory cardiac receptors in left ventricle of the dog.

The purpose of this study was to determine the relative magnitudes of the reflex effects mediated by sensory endings in the left ventricle activated by intracoronary injection of nicotine or veratridine into left anterior descending (LAD) or circumflex (Cx) coronary arteries in the dog. Injection of nicotine or veratridine into the Cx consistently resulted in larger decreases in heart rate, arterial pressure, and in gracilis perfusion pressure than were observed following injection of the same dose into the LAD. Vagotomy abolished the cardioinhibitory and vasodepressor responses to intracoronary nicotine or veratridine. The weight of left ventricle perfused by LAD or Cx was not different (43.5 +/- 1.65 and 44.5 +/- 2.2 g, respectively. These data indicate that chemical activation of sensory endings with vagal afferents in the inferoposterior left ventricle of the dog results in larger cardionhibitor and vasodepressor responses than result from activation of respects in the anterior left ventricle. Further, these data provide strong evidence that these sensory endings which are chemically activated are preferentially distributed to the inferoposterior left ventricle.

Afferent Pathways↗
PubMed1978

Effects of indomethacin on the vascular abnormalities of Bartter's syndrome.

We examined the hypothesis that the vascular abnormalities of Bartter's syndrome are due to excess production of prostaglandin. Balance studies and vascular reactivity studies were performed before and after indomethacin (200 mg/day) in a patient with well-documented Bartter's syndrome. During indomethacin, potassium balance became positive, serum potassium rose from 2.1--3 mEq/1 in the absence of potassium supplementation, plasma renin activity decreased from 55--3.2 ng/day and peripheral plasma PGA-like activity fell from 1460 +/- 220 to 456 +/- 71 pg/ml. Before indomethacin, forearm vasoconstrictor responses to brachial arterial infusions of angiotensin II, norepinephrine and to neurogenic reflex stimulation elicited by lower body suction were greatly depressed compared to those of normal subjects. During indomethacin these responses were restored to normal. The dose of intravenous angiotensin II required to increase diastolic blood pressure 20 mm Hg decreased from 160--30 ng/kg/min. These data support the hypothesis that the vascular insensitivity to exogenous angiotensin II, norepinephrine and to neurogenic reflex stimulation observed in this patient with Bartter's syndrome is due to excess prostaglandin. Moreover, stimulation of the renin-angiotensin-aldosterone system in this syndrome appears to be a compensatory adaptation to excess prostaglandin production.

Adult↗