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Biomedical subjects

J Holtz

Publications and source records attributed to J Holtz.

At least 109 records · Page 6Linked to original sources
PubMed1987

Dilation of epicardial arteries in conscious dogs induced by angiotensin-converting enzyme inhibition with enalaprilat.

Vasodilators may provoke myocardial ischemia in patients with coronary heart disease. Therefore, we analyzed in conscious dogs the effect of angiotensin-converting enzyme (ACE) inhibition by enalaprilat on parameters potentially important to provocation of myocardial ischemia, such as sympathetic activity, myocardial oxygen consumption, and vascular tone in coronary conduit and resistance vessels. Under normal sodium intake (2-4 mEq/kg/day), enalaprilat (0.03 and 0.3 mg/kg i.v. during 5-min infusion with 30-min intervals, n = 8) did not modify the norepinephrine release rate into plasma (a parameter of overall sympathetic activity). The higher dosage reduced myocardial oxygen consumption (to 87 +/- 2% of control), mean arterial pressure (MAP) (to 90 +/- 1%) and coronary conduit artery tone (normalized delta diameter: +3.2 +/- 0.7%) without dilating coronary resistance vessels. Following renin-angiotensin activation by sodium deprivation (3 X 1 mg/kg furosemide plus 7 days sodium intake less than 0.2 mEq/day), enalaprilat similarly lowered myocardial oxygen consumption and reduced vascular tone both in coronary conduit (normalized delta diameter: +4.0 +/- 0.9%) and resistance vessels (delta coronary flow: +45 +/- 12%). Although MAP declined to 76 +/- 6%, heart rate and norepinephrine release rate were not modified significantly. We propose that the dilation of epicardial arteries results from a direct intramural action. Enalaprilat seems unlikely to provoke myocardial ischemia even in states with a strongly activated renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Long-term nitroglycerin treatment: effect on direct and endothelium-mediated large coronary artery dilation in conscious dogs.

We examined the effect of nitroglycerin (GTN) tolerance on an important determinant of nitrate-antianginal action, large coronary artery dilation, in 11 chronically instrumented conscious dogs. In addition, endothelium-mediated coronary artery dilation was studied because this shares a common dilator pathway with the nitrates, i.e., activation of soluble guanylate cyclase. With long-term GTN (1.5 micrograms/kg/min iv for 5 days) the diameters of the left circumflex and anterior descending coronary arteries showed an initial increase of 8.2 +/- 0.3% and 10.8 +/- 0.9%, respectively, returning to control levels by the second to third day of treatment. On days 4 and 5, the dose-response relations for GTN-induced epicardial artery dilation were shifted (p less than .01) to 17- to 20-fold higher doses. However, there was no attenuation of epicardial artery dilation induced by SIN-1 (n = 7), another activator of guanylate cyclase, or of endothelium-mediated dilation assessed both as flow-dependent dilation (n = 7) and as direct intra-arterial acetylcholine-induced dilation (n = 4). In addition, there was no clear tolerance to the peripheral vascular actions of GTN responsible for reflex tachycardia and increased coronary flow. We conclude that a moderate degree of nitrate tolerance to epicardial artery dilation does not affect the responsiveness to other exogenous or endogenous activators of guanylate cyclase. However, this tolerance to epicardial artery dilation, together with the maintenance of peripheral vascular actions that can induce reflex tachycardia, result in a potentially unfavorable balance of GTN effects.

Acetylcholine↗
PubMed1987

Inhibition of sympathoadrenal activity by atrial natriuretic factor in dogs.

In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Atrial natriuretic hormone in the human].

The muscle cells of cardiac atria contain many secretory granula with a prohormone of 126 amino acids (ANF(1-126)). Distension of the atria causes exocytosis of the granula with cleavage of the prohormone into the hormone ANF(99-126) or alpha-ANP and the N-terminal fragment ANF(1-98) with an as yet unknown role. The plasma concentration of the hormone in normal man is in the range of 10 pM (30 pg/ml) with a plasma half-life of several minutes and a release rate of 2-3 ng/kg per minute. The plasma concentration changes in parallel with the intake of sodium chloride and is elevated acutely by all interventions which increase the blood volume, or which cause its redistribution towards the cardiopulmonary compartment. Infusions of the hormone cause diuresis and natriuresis, inhibition of the renin-angiotensin-aldosterone system and of sympathetic activity and augmentation of tissue filtration. Thus, a hormonal feedback loop for cardiac unloading by limiting the plasma volume could be assumed. However, the ANF infusion rates necessary for eliciting these actions in man induce ANF plasma concentrations above physiological levels. On the other hand, a physiological role of the hormone in this regulation is suggested by observations during long-term administration of the hormone, which demonstrate actions of the hormone at physiological plasma levels. Furthermore, experiments with injection of ANF antibodies indicate a synergistic action of ANF, together with reflexes in response to atrial distension. ANF acts by activating specific high affinity membrane receptors, resulting in intracellular cGMP formation and cGMP release into plasma and urine. These ANF receptors are "down-regulated" by infusions of the hormone and by chronic volume expansion. In fetal circulation and in congestive heart failure, there is also augmented prohormone synthesis in the cardiac ventricles, which may then contribute to the release of the hormone. Although during cardiac failure the ANF plasma levels are augmented up to 30-fold, and the atrial prohormone content is reduced, there is no indication for an exhaustion of hormone synthesis or for resetting of stimulated hormone release. In addition to its role as a peripheral hormone for "cardiac unloading", ANF occurs in the central nervous system as a neuropeptide, which might also be involved in blood pressure and volume regulation.

Atrial Natriuretic Factor↗
PubMed1987

[Postoperative hemoglobin course and septic complications following stomach resection].

Preoperative and postoperative haemoglobin curves were studied in male patients, following two-third gastrectomy. A group with early septic complications was compared to one without. The groups were comparable for age distribution and pathological patterns (ulcer/gastric stenosis and carcinoma). Preoperative haemoglobin mean values were a the lower normal limit and dropped to 10.8 g/dl in the group with complications on the fifth day from surgery, but stayed constant at 12 g/dl in the control group, as of the second postoperative day. Haemoglobin dropped to mean values around 11 g/dl immediately after surgery in patients with severe complications, such as suture dehiscence. All groups deviated clearly from normal Hb.

Female↗
PubMed1986

In vivo atrial peptide-venodilation: minimal potency relative to nitroglycerin in dogs.

Venodilation is thought to contribute to the hemodynamic actions of atrial peptides. Therefore, we measured the effective vascular compliance (EVC) as a parameter of overall venous tone in 7 pentobarbital anesthetized dogs under autonomic blockade during i.v. infusions of rat atriopeptin II (AP II, up to 100 pmol/kg/min), rat alpha-atrial natriuretic factor, and nitroglycerin (GTN). AP II lowered mean arterial pressure by reducing peripheral vascular resistance with a threshold between 3 and 10 pmol/kg/min (but was ineffective in anesthetized or conscious dogs without autonomic blockade). Neither atrial peptide altered EVC, while GTN augmented EVC and caused a 4.6-fold larger reduction of central venous pressure than AP II at equihypotensive dosage. These findings, with infusion rates probably close to endogeneous release, reveal a vasodilator potency of atrial peptides, which is restricted to systemic arterioles without affecting venous tone.

Animals↗
PubMed1986

Altered spectrum of nitroglycerin action in long-term treatment: nitroglycerin-specific venous tolerance with maintenance of arterial vasodepressor potency.

The study of venodilator tolerance to nitroglycerin has been complicated by reflex compensation and by problems in analyzing venous tone in the presence of multiple determinants of venous pressure. We assessed venous tone as total effective vascular compliance (TEVC) under autonomic blockade in six dogs, in the nontolerant state, and during a 5 day infusion of nitroglycerin (1.5 micrograms/kg/min). Under long-term treatment, baseline TEVC was unaffected and the nitroglycerin dose-response relationship for TEVC was shifted to greater than 10-fold higher doses, whereas baseline mean arterial pressure (MAP) was lowered by 17 +/- 3 mm Hg without any shift in nitroglycerin responsiveness. This lowering of MAP was observed only after autonomic blockade. In six additional dogs instrumented with aortic flow probes, nitroglycerin (1.5 micrograms/kg/min) induced a 15 +/- 1% decline in peripheral vascular resistance (PVR) under autonomic blockade, but with reflexes intact these dogs showed no change in PVR and a 21 +/- 10% increase in norepinephrine release rate. We conclude that modest long-term exposure to nitroglycerin results in tolerance to its venodilating effects, whereas arteriolar action is maintained. This tolerance-induced shift in action from venous toward arteriolar dilation is normally masked by compensatory reflexes.

Animals↗
PubMed1986

Crucial role of endothelium in the vasodilator response to increased flow in vivo.

Experiments were designed to investigate the importance of vascular endothelium in the vasomotor response to increases in flow as observed in conduit arteries (flow-dependent dilation). The diameter changes of femoral arteries (sonomicrometry) in response to increases in flow before and after endothelial damage procedures were studied in 23 dogs anesthetized with sodium pentobarbital. The functional integrity of the endothelial cells underneath the diameter sensors was tested by intra-arterial acetylcholine (local acetylcholine dilation) applied proximally to the sensors while a constant flow was maintained. Unilateral augmentation of femoral arterial flow (4.6 +/- 1.9-fold) induced by peripheral vasodilation or by arteriovenous shunt, elicited dilation (increase in diameter, 116 +/- 91 microns) in 18 of 23 dogs, whereas the diameter of the contralateral control artery was not affected. Mechanical removal of the endothelial cells by means of a balloon catheter abolished both the flow-dependent dilation and the local acetylcholine dilation, whereas the vasomotor responses to norepinephrine and nitroglycerin were not affected. Brief perfusions (1 minute) of the arteries with cell-free hydrogen peroxide solution (90 mM) also abolished the flow-dependent dilation and attenuated the local acetylcholine dilation (by 27 +/- 19%; p less than 0.02), while the responses to norepinephrine and nitroglycerin were not altered. These results suggest that endothelial cells act as mediators of flow-dependent dilation.

Acetylcholine↗
PubMed1986

Postsynaptic alpha 1- and alpha 2-adrenergic receptors in adrenergic control of capacitance vessel tone in vivo.

The involvement of postsynaptic alpha 2-adrenergic receptors in the adrenergic constriction of the capacitance vessels was studied in anesthetized, spontaneously breathing dogs under ganglionic blockade (hexamethonium, 10 mg/kg + 10 mg/kg/hr; methylatropine, 0.5 mg/kg). Effective vascular compliance was measured as an indicator of venous tone (blood volume was varied by +/- 4 ml/kg in an 11-minute cycle of infusion, withdrawal, withdrawal, and reinfusion) and was calculated from the correlation between the observed changes in central venous pressure and the changes in blood volume. Sympathetic activity and central venous pressure were lower and effective vascular compliance was higher than values in untreated conscious dogs. The alpha 2-agonist UK 14,304 (5-bromo-6-[imidazolin-2-ylamino]-quinoxaline; 0.04 and 0.12 micrograms/kg/min; n = 6) dose-dependently lowered compliance and increased central venous pressure to levels found in conscious dogs, as did the alpha 1-agonist methoxamine (10 and 30 micrograms/kg; n = 6). Rauwolscine (alpha 2-antagonist), 0.3 mg/kg, significantly attenuated the effects of UK 14,304, but not those of methoxamine, while prazosin (alpha 1-antagonist), 0.12 mg/kg, attenuated the effects of methoxamine, but not those of UK 14,304 (n = 6 each). Under beta-blockade (nadolol, 2 mg/kg; n = 12) venous tone was increased to about physiological levels by norepinephrine, 0.15 micrograms/kg/min i.v., or by neuronal norepinephrine release induced by tyramine, 10 micrograms/kg/min i.v. These increases were significantly attenuated by prazosin as well as by rauwolscine and were abolished by a combination of both. These results indicate that postsynaptic alpha 2-adrenergic receptors (in addition to alpha 1-adrenergic receptors) are functional in the venous system in vivo and contribute substantially to adrenergic sympathetic and humoral regulation of venous tone.

Adrenergic alpha-Antagonists↗
PubMed1985

Role of the endothelium in the vasomotor effects of angiotensin I in isolated arteries with or without inhibition by MK 422.

We investigated in the isolated rabbit aorta the ability of the endothelium to attenuate the vasoconstrictor effects of angiotensin (ANG) I and II. After preincubation with enalaprilat, which inhibited the conversion of ANG I to ANG II by 80%, the contractile response to ANG I (10(-8) to 10(-6) mol/l) was significantly greater in aortae which were endothelium-denuded compared with endothelium-intact segments. There was no such difference for ANG II (10(-10) to 3 x 10(-8) mol/l). We conclude that an endothelium-mediated dilatation is part of the net vasomotor action of ANG I.

Angiotensin I↗
PubMed1984

Development of specific tolerance to nicotine infusions in dogs on chronic nicotine treatment.

Chronic smoking in humans and continuous nicotine application in animals do not induce hypertension, although the acute effects of nicotine are sympathoadrenal activation and elevation of blood pressure. In conscious dogs with a carotid artery loop preparation, we studied whether chronic nicotine application induced tolerance to the acute effects of nicotine test infusions. Nicotine was applied as salicylate via subcutaneously implanted osmotic minipumps at a dosage of 1 microgram/kg/min = 1.44 mg/kg/day, corresponding to heavy smoking in humans. Chronic treatment in eight dogs for 5-8 weeks did not modify resting heart rate and plasma levels of free catecholamines, but significantly increased plasma levels of conjugated dopamine by 100%. Mean arterial pressure at rest was elevated in the 2nd week by 6mm Hg, but did not increase further. Sham treatment (n = 8, sodium salicylate in equivalent dosage) was without effect. Acute test-infusions of nicotine (3 and 10 micrograms/kg/min i.v.) caused acute rises in mean arterial pressure (by 12 and 28 mm Hg), heart rate (by 9 and 18 bpm), plasma norepinephrine (by 36 and 68%), plasma epinephrine (by 110 and 180%) and led to plasma nicotine levels of 31 and 95 ng/ml. Chronic nicotine treatment attenuated the hemodynamic and partially abolished the hormonal effects without affecting the nicotine plasma levels obtained with these test infusions, but it did not modify the hemodynamic effects of a norepinephrine test infusion. The data demonstrate the development of a specific, reversible tolerance to the acute sympathoadrenal activation by nicotine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Attenuation of sympathetic vasoconstriction by nifedipine: the role of vascular alpha 2-adrenoceptors.

The effects of nifedipine on hindlimb vasoconstriction caused by norepinephrine infusion and sympathetic stimulation (0.1-1.0 Hz) were compared in dogs given 0.12 mg/kg prazosin or 0.3 mg/kg rauwolscine. Constrictions due to stimulation or norephinephrine with prazosin, presumed to be mediated by vascular alpha 2-adrenoceptors, were significantly attenuated by 30 micrograms/kg nifedipine, while constrictions with rauwolscine, presumably alpha 1-mediated, remained unaffected. These data support the hypothesis that the antihypertensive effect of calcium antagonists is based upon interference with alpha 2-mediated sympathetic vasoconstriction.

Animals↗
PubMed1983

[Do lowered hemoglobin and hematocrit levels have a favorable effect on early septic complications in colorectal surgery?].

A group of 114 colorectal resections was investigated for preoperative haemoglobin and haematocrit in relation to postoperative septic complications. The group subdivided in men and women with and without complications were comparable in respect of their age and their diseases. There were significant differences in the preoperative levels of Hb and Ht in the groups with and without postoperative septic complications (p less than 0.05). The mean values were 14.7 g/dl for men with postoperative complications and 13.7 g/dl for those without any complications. The corresponding Ht-values were 45% vs. 42%. The mean values of Hb for women were 13.9 g/dl in the groups with postoperative complications and 12.9 g/dl in those without any complications (Ht-values 43% resp. 39%).

Adult↗
PubMed1983

Two dilatory mechanisms of anti-anginal drugs on epicardial coronary arteries in vivo: indirect, flow-dependent, endothelium-mediated dilation and direct smooth muscle relaxation.

Potential mechanisms of antianginal drugs involve preload and afterload reduction and a dilation of large conduit coronary arteries without a substantial concomitant dilation of the coronary resistance vessels. We analyzed the dilatory mechanism. It consists of two independent components: a direct effect on the arterial smooth muscle and an indirect, endothelium-mediated, shear-stress-dependent effect on the arterial vasculature. Therefore, we tested the relative contribution of these two components in the dilatory response of large coronaries to various antianginal drugs. In chronically instrumented dogs, the outer diameters and the flow in two coronary branches (left circumflex and descending) were registered continuously. A pneumatic occluder implanted distally to the site of the diameter measurements was used in one branch to control flow rates or to maintain constant flow, independent of arteriolar dilation. Increments in flow of more than 100% were elicited by i.v. injections of adenosine, dipyridamole, nifedipine, diltiazem, verapamil, nitroglycerin, ISDN, and molsidomine. All these agents induced a slowly developing dilation of the epicardial coronary arteries (by more than 100 microns), which reached its maximum 90 s after the onset of the increase in flow (while arterial pressure fell). When flow in one branch was experimentally kept constant, the epicardial dilation by adenosine and dipyridamole was completely offset, while it remained unaffected in the control branch with unrestricted flow. Thus, the dilation of the coronary artery by these two drugs is based on the indirect component, caused by the flow-dependent mechanism, in contrast to nitroglycerin-, molsidomine-, and ISDN-induced dilations, which were not affected at all by experimentally limiting the flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1983

[Surgical treatment of hiatal hernia].

125 patients suffering from hiatal hernia were seen at the Surgical Clinic of Bonn-University between 1963 and 1977. 76 patients underwent surgery and could be followed-up. Our treatment of choice is gastropexy.

Adolescent↗