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Biomedical subjects

P I Korner

Publications and source records attributed to P I Korner.

At least 37 records · Page 2Linked to original sources
PubMed1977

Autonomic blockade and the Valsalva maneuver in patients on maintenance hemodialysis: a hemodynamic study.

Hemodynamic studies were performed at two levels of dietary sodium intake (10 mmoles/day and 100 mmoles/day for 14 days) in a group of patients (with retained kidneys) on chronic hemodialysis. Plasma renin activity and aldosterone, plasma, and extracellular fluid (ECF) volumes were measured while the patient were at rest. Cardiac output, mean intraarterial pressure, and the calculated total peripheral resistance index were recorded while the patients were at rest and during acute "total" autonomic blockade. On the sodium diet of 10 mmoles/day, normotensive and hypertensive patients had similarly low total blood volumes, low-normal ECF volumes, and similar levels of plasma renin and aldosterone. The resting cardiac output was increased in both groups, but the total peripheral resistance was increased only in the patients with hypertension, in whom peripheral resistance was inappropriately high for the degree of anemia. Six hypertensive patients were studied on both diets. The resting mean arterial pressure was greater on the sodium diet of 100 mmoles/day than on the 10 mmoles/day diet, accompanied by increased in plasma volume, extracellular fluid volume, and cardiac output, but no change in peripheral resistance. During autonomic blockade on either diet, there was a marked fall in blood pressure in the patients with hypertension. This was mainly due to a fall in peripheral resistance which reached levels similar to those seen in the normotensive patients whose resistance was unaltered by blockade. Autonomic factors appear to contribute to the elevated peripheral resistance of hypertensive dialysis patients. In these patients, the effect of a high sodium diet, at least over the time-scale studied here, is to increase blood pressure and cardiac output, without the change in peripheral resistance expected from autoregulation.

Adult↗
PubMed1977

Leakage of dl-propranolol from cerebrospinal fluid to the bloodstream in the rabbit.

Intracerebroventricular (i.c.v.) injection of 500 microgram of dl-propranolol in the conscious rabbit in a rise in mean arterial pressure followed by a small but significant fall (3.2 +/- 1.4 mm Hg between 2 and 4 hours after injection), as has been observed by others. The same dose injected i.v. resulted in a lowering of mean arterial pressure of 6.0 +/- 2.4 mm Hg between 2 and 4 hours after injection. After i.c.v. injection there was a rapid rise in plasma propranolol concentration. Ten minutes after i.c.v. injection the concentration of 80% of the level reached after giving the same dose i.v. After i.c.v. injection there was significant blockade of cardiac beta adrenoreceptors for at least 2 hours. This blockade was determined from the degree of attenuation of isoproterenol-induced tachycardia in rabbits subjected to presynaptic sympathetic nerve block with guanethidine and to vagal block with methscopolamine. Because of the rapid leakage of propranolol from cerebrospinal fluid to plasma it is not possible by means of the technique of i.c.v. injection of the drug to differentiate between central nervous and systemic mechanisms contributing to the lowering of blood pressure.

Animals↗
PubMed1976

Double-blind factorial trial of prindolol and hydrochlorothiazide in hypertension.

The antihypertensive actions of the beta-adrenergic blocking agent, prindolol, and of the diuretic, hydrochlorothiazide, were analysed in a double-blind randomized 2 X 2 factorial trial in 16 patients. There were four eight-week phases in which patients received prindolol alone, hydrochlorothiazide alone, prindolol plus hydrochlorothiazide in combination, and no treatment. Both drugs were given in fixed doses: prindolol, 10 mg three times per day; hydrochlorothiazide, 50 mg per day. Blood pressure was measured weekly, alternately at the outpatient clinic and at home. Supine mean arterial pressure (MAP) in resting patients fell from 127 mm Hg in the placebo phase to 117 mm Hg with hydrochlorothiazide alone, 116 mm Hg with prindolol alone, and 111 mm Hg with the combination of prindolol and hydrochlorothiazide. (The standard error of difference between treatments was +/-3-58). A mean factorial effect of -7 mm Hg for hydrochlorothiazide (P less than 0-01) and -8 mm Hg for prindolol (P less than 0-01) was obtained, and the two drugs acted in an additive manner. The effects on standing blood pressure in resting patients were similar. No serious side effects were noted.

Adult↗
PubMed1976

Effect of beta-adrenergic blockade with alprenolol on ST-segment depression and circulatory dynamics during exercise in patients with effort angina.

1. Nine subjects with severe coronary artery disease were studied during graded "sprint" and "steady-state" exercise before and after intravenous administration of the beta-receptor antagonist alprenolol. During "sprint" workload was increased every minute until maximum work capacity (Wmax) was reached. "Steady-state" exercise was performed at work rates of 0.250, 0.50, and 0.75 of each subject's sprint Wmax. Variables measured included ST-segment depression, changes in heart rate, blood pressure, respiratory gas exchange, and arterial blood composition. Cardiac output (indirect Fick) was measured during "steady-state" exercise. 2. Alprenolol did not alter Wmax during "sprint" but reduced the incidence of angina in both types of exercise. After the drug work capacity was limited by symptoms and signs suggestive of mild left ventricular failure. 3. The relationship between workload (normalized in terms of Wmax) and ST-segment depression was curvilinear. Under control conditions a given rate of work during "steady-state" exercise was assocaited with more marked ST-segment depression than during "sprint". Alprenolol displaced the work-ST-depression curve to the right in each type of exercise; now a given rate of work produced similar ST-depressing during "steady-state" and "sprint" exercise. 4. Alprenolol attentuated the exercise tachycardia during both types of exercise. Cardiac output was lower in "steady-state" exercise after the drug than under control conditions. Metabolic effects included significant reduction in body oxygen consumption after alpreprenolol at 0.25 Wmax and diminished arterial lactate at 0.75 Wmax. The beneficial effects of the drug thus appeared to involve not only cardiac but peripheral effects on beta receptors. 5. Before alprenolol cardiac output was relatively fixed at all workloads, but after the drug there was a work-related rise in output in five out of nine subjects. Comparison with data in normal subjects suggested that in anginal subjects cardiac output at low "steady-state" workloads was inappropriately high.

Adult↗
PubMed1976

Assessment of autonomic and non-autonomic components of resting hindlimb vascular resistance and reactivity to pressor substances in renal hypertensive rabbits.

1. Hindlimb vascular resistance (HVR) was measured before and after pharmacological autonomic blockade in unanesthetized renal cellophan-wrap hypertensive or normotensive rabbits with previously implanted Doppler ultrasonic flowmeters. 2. When the blood pressure was restored to resting values after autonomic block, the elevated resting HVR in the hypertensive rabbits was entirely accounted for by an increased non-autonomic component (i.e. HVR after block). If the pressure was not restored after block the autonomic component (i.e. resting HVR minus non-autonomic HVR) was overestimated and the non-autonomic component was underestimated. 3. During maximum vasodilatation the minimum HVR was significantly higher in the hypertensive rabbits than in the normotensive group, probably due to structural differences of resistance vessels. 4. Reactivity of the hindlimb bed to noradrenaline, angiotensin II and vasopressin injections was approximately twice as great in the hypertensive rabbits as in the sham-operated group, probably as a consequence of the structural changes.

Animals↗
PubMed1976

Cardiac output changes during experimental renal hypertension in the rabbit.

1. The haemodynamic changes during the development of hypertension in rabbits have been studied for 1 week before and 4-5 weeks after sham-operation (thirteen rabbits) or bilateral renal cellophan wrapping (thirteen rabbits), Doppler flowmeters being used to measure cardiac output. 2. There was a significant but transient rise in cardiac output on post-operative day 4 in six of thirteen sham-operated rabbits and six of thirteen renal-wrap rabbits before development of hypertension. Both groups showed the same rise in mean cardiac output of 10%. The reise in cardiac output was more transient than in other species, and was not essential for subsequent development of hypertension.

Animals↗
PubMed1976

Valsalva vasoconstrictor reflex in human hypertension in after beta-adrenoreceptor blockade in conscious rabbits.

1. A Valsalva-like manoeuvre was used to elicit graded rises in total peripheral resistance (TPR) in conscious rabbits. The rises were reflex and mediated through sympathetic constrictors. Propranolol infused at different rates reaching plasma concentrations up to 240 (SEM 33) ng/ml had no effect on this reflex but reduced mean arterial pressure. However, the response was attenuated by clonidine in a dose-dependent manner. 2. Valsalva manoeuvres were used to elicit graded sympathetically mediated rises in TPR index in twenty-nine subjects with mean arterial pressure ranging from 75 to 165 mmHg. Absolute sensitivity of the constrictor response increased with rising resting TPR index, resulting in some enhancement of constrictor responses in the hypertensive subjects. It seems likely that non-autonomic factors (e.g. vessel structure) rather than hyperactive neural constrictor effects are involved in the enhanced constrictor responses in essential hypertension.

Adrenergic beta-Antagonists↗
PubMed1976

Quantitative effects of timolol and hydrochlorothiazide on blood pressure, heart rate and plasma renin activity: results of a double-blind factorial trial in patients with essential hypertension.

1. The anti-hypertensive actions of timolol and hydrochlorothiazide were analysed in a double-blind 2 x 2 factorial trial in twenty patients with essential hypertension. Each patient went through four phases of 8 weeks in randomized order, receiving timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and placebo. 2. Supine mean arterial pressure fell from 119 mmHg in the placebo phase, to 110 mmHg during the thiazide phase, 106 mmHg during the timolol phase, and to 101 mmHg during the combined timolol plus hydrochlorothiazide phase. 3. Factorial analysis revealed that the hypotensive actions of the beta-receptor-blocking drug and the diuretic were additive, without any synergism or antagonism. 4. Plasma renin activity measured in ng 3 h-1 ml-1 rose from 5-02 in the placebo phase to 9-54 in the diuretic phase, but fell to 1-79 in the beta-receptor blockade. It was unchanged in the combined therapy phase, despite the greater drop in blood pressure. These results suggest that the fall in plasma renin activity during beta-receptor blockade is of little importance in the hypotensive action of beta-receptor-blocking drugs.

Adult↗
PubMed1976

Reflex and mechanical circulatory effects of graded Valsalva maneuvers in normal man.

In 17 normal subjects we studied the changes evoked by five levels of expiratory pressure (EP) ranging from 2.5 to 30 mmHg in a number of circulatory variables during the last 10 s of a 30-s Valsalva maneuver. Variables studied included mean arterial (MAP) and pulse (PP) pressures; right atrial (RAP) and peripheral vein (PVP) pressures; cardiac output (CO); total peripheral resistance (TPR) and heart rate (HR). EP-circulatory response curves were obtained in each subject a) before autonomic block; b) after cardiac effector block (atropine + propranolol); c) after "total" autonomic block (atropine + propranolol; guanethidine + phentolamine). Mechanical effects were determined from results during "total" autonomic block. They included EP-related rises in RAP and PVP each to about 0.7 mmHg/mmHg applied EP, and falls in CO, MAP, and PP to levels of approximately 50%, 70%, and 80% of resting respectively at EP 30 mmHg, but no changes in TPR and HR. Reflex effects included EP-related rises in HR and in TPR and in MAP, to levels of 160%, 160%, and 115% of resting respectively at EP 30 mmHg. The afferent input profile is probably complex, and the role of the different receptor groups may vary at the different levels of EP.

Atrial Function↗
PubMed1976

Changes in cardiac output and total peripheral resistance during development of renal hypertension in the rabbit: lack of confomity with the autoregulation theory.

Serial measurements of cardiac output (CO), mean arterial pressure (MAP), heart rate, and total peripheral resistance (TPR), were made on unanesthetized rabbits with previously implanted Doppler flowmeters. After 2 days of control measurements the rabbits were subjected alternatively to bilateral renal cellophane wrapping (wrap group) or to sham operation and additional measurements were made 1, 2, 4, 8, 16, 25, and 32 days after operation. During the 1st week after operation changes in CO were identical in the wrap and sham-operated groups, with an overall increase to a value of 110% of control on day 4 (P less than 0.05). Thereafter CO fell gradually, reaching 75% of control by day 32 in the wrap group, but only 95% of control in the sham-operated group. When CO was expressed per unit of body weight the latter differences were somewhat reduced, but still were significant. In wrap animals MAP and TPR rose progressively to 155% and 194% of control by day 32. In the sham-operated group the corresponding increases to 108% and 118% of control were significantly smaller. The MAP and TPR of the renal wrap rabbits exceeded the values in sham-operated rabbits, even over the 1st week after operation, by an average for MAP of 8.6 +/- 1.4% (P less than 0.001), and for TPR of 8.0 +/- 2.5% (P = 0.01). The results suggest that the changes in CO during the 1st week were a nonspecific consequence of the preceding wrap or sham operation. They bore no apparent relationship to the subsequent development of the hypertension which was "resistance-mediated" from the earliest stages. We conclude that the present findings for the rabbit differ from those reported for other species and do not conform to the changes predicted by the autoregulation theory of the pathogenesis of hypertension.

Animals↗
PubMed1975

Central nervous system control of cardiorespiratory nasopharyngeal reflexes in the rabbit.

The role of different central nervous regions in the reflex apnea, bradycardia, and mesenteric vasoconstriction evoked by nasopharyngeal stimulation with cigarette smoke was examined in unanesthetized shamoperated, thalamic, and pontine rabbits with intact and sectioned carotid sinus and aortic nerves (CS and AN). Apnea occurred in all preparations. In pontine animals with intact CS and AN, the heart rate response was reduced but not the mesenteric vasoconstriction. The role of suprabulbar and bulbospinal regions became more apparent when individual components of the input profile were examined in animals with controlled ventilation. The bradycardia and mesenteric vasoconstriction evoked by apnea without smoke, but not by smoke without apnea, were reduced in pontine animals. Prior section of the CS and AN attenuated the response in all neural preparations but to the least extent when cerebral hemispheres were intact. The data indicate that the respiratory reflex is predominantly integrated at bulbospinal sites, but the cardiovascular reflex is integrated at both bulbospinal and suprabulbar sites, or is integrated at bulbospinal and modulated from suprabulbar sites.

Animals↗
PubMed1975

The action of clonidine on the baroreflex control of heart rate in conscious animals and man, and on single aortic baroreceptor discharge in the rabbit.

Changes in mean arterial pressure (M.A.P.) have been produced in conscious rabbits by inflation of balloon cuffs previously implanted round the inferior vena cave and aorta; Sigmoid stimulus/response curves (M.A.P./Heart Period, H.P.) were constructed. Clonidine caused a striking dose dependent increase in gain of the reflex arc in both normal rabbits and rabbits with renal hypertension. The largest effect was upon vagal motorneurones but a similar but smaller effect was present in vagotomised animals. Similar changes in the baro-reflex arc were produced by injection of very much smaller doses of clonidine into the lateral cerebral ventricle. Recordings made from single aortic baroreceptor fibres in anaesthetised rabbits showed again a dose dependeent sensitisation. These results suggest that the bradycardia caused by clonidine is largely mediated via an action in the brain on the baroreflex arc, with an additional action on the baroreceptors themselves. Preliminary results in normal man show a similar increase in the gain of this reflex after intravenous clonidine (150 mug).

Animals↗
PubMedDate not supplied

Effects of histamine bolus injections and continuous infusions on the H1- and H2-receptors in the hindlimb vessels of the rabbit.

1. Hindlimb vascular resistance (HVR) was continuously measured after pharmacological block of the autonomic effectors in unanesthetized rabbits with previously implanted Doppler ultrasonic flowmeters. 2. Histamine bolus injections caused a dose-related short lived fall in HVR followed by a more sustained rise. The fall was due to H2-receptor stimulation (blocked by burimamide or metiamide) and the rise to H1-receptor stimulation (blocked by mepyramine). At the doses of histamine tested the magnitude of the H1-mediated vasoconstriction had a larger peak effect than the H2-mediated vasodilatation. 3. Histamine infusions up to 200 microgram kg-1 min-1 did not alter HVR significantly but both increases and decreases in HVR were observed after giving H2- or H1-antagonists, respectively. 4. From the double reciprocal plots of 1/peak HVR change and 1/dose of histamine the magnitude of the predicted H1- and H2-mediated peak HVR effects at large doses were the same. This suggested that the number of H1- and H2-receptors were similar in the hindlimb vascular bed, in agreement with the infusion data.

Animals↗
PubMedDate not supplied

Cardiovascular and respiratory effects of carotid body stimulation in the monkey.

1. The carotid bodies were stimulated in the anaesthetized pig-tailed macaque monkey (M. nemestrina) using (i) brief injections of cyanide or CO2-equilibrated bicarbonate solution into a common carotid artery, and (ii) longer perfusion with hypoxic hypercapnic blood in vascularly isolated chemoreceptor preparations. 2. In spontaneously breathing animals brief stimuli (thirty-one tests, seven monkeys) consistently increased pulmonary ventilation (by 97 +/- 10% of control), slowed the heart rate (the pulse interval increasing by 36 +/- 7.5%), and increased femoral vascular resistance (by 44 +/- 7%). 3. More sustained chemoreceptor stimulation with asphyxial blood (nineteen tests, five monkeys) increased ventilation by 187 +/- 23%, but transient bradycardia occurred in only eight of nineteen tests and was followed by tachycardia; in the remaining tests, only tachycardia occurred. After 20--40s, the pulse interval was 5.8 +/- 0.9% below the control level. Femoral vascular resistance either increased (five tests, two animals) or decreased (six tests, two animals). 4. Evidence is presented that in the monkey the autonomic effects of chemoreceptor stimulation are influenced by the level of respiratory activity with bradycardia and vasoconstriction occurring when the level is low, and tachycardia and vasodilatation when it is high. 5. The interaction of autonomic responses resulting from carotid body stimulation and from mechanisms initiated by the concomitant hyperventilation are qualitatively similar in the monkey and in subprimate species, although there may be quantitative differences such as would account for the species differences to distrubances produced, for instance, by arterial hypoxia.

Animals↗